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Biomedical subjects

M Leong

Publications and source records attributed to M Leong.

14 recordsLinked to original sources
PubMed2005

Killed but metabolically active microbes: a new vaccine paradigm for eliciting effector T-cell responses and protective immunity.

We developed a new class of vaccines, based on killed but metabolically active (KBMA) bacteria, that simultaneously takes advantage of the potency of live vaccines and the safety of killed vaccines. We removed genes required for nucleotide excision repair (uvrAB), rendering microbial-based vaccines exquisitely sensitive to photochemical inactivation with psoralen and long-wavelength ultraviolet light. Colony formation of the nucleotide excision repair mutants was blocked by infrequent, randomly distributed psoralen crosslinks, but the bacterial population was able to express its genes, synthesize and secrete proteins. Using the intracellular pathogen Listeria monocytogenes as a model platform, recombinant psoralen-inactivated Lm DeltauvrAB vaccines induced potent CD4(+) and CD8(+) T-cell responses and protected mice against virus challenge in an infectious disease model and provided therapeutic benefit in a mouse cancer model. Microbial KBMA vaccines used either as a recombinant vaccine platform or as a modified form of the pathogen itself may have broad use for the treatment of infectious disease and cancer.

Animals↗
PubMed2001

SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport.

The epithelial Na+ channel (ENaC) constitutes the rate-limiting step for Na+ transport across tight epithelia and is the principal target of hormonal regulation, particularly by insulin and mineralocorticoids. Recently, the serine-threonine kinase (SGK) was identified as a rapidly mineralocorticoid-responsive gene, the product of which stimulates ENaC-mediated Na+ transport. Like its close relative, protein kinase B (also called Akt), SGK's kinase activity is dependent on phosphatidylinositol 3-kinase (PI3K), a key mediator of insulin signaling. In our study we show that PI3K is required for SGK-dependent stimulation of ENaC-mediated Na+ transport as well as for the production of the phosphorylated form of SGK. In A6 kidney cells, mineralocorticoid induction of the phosphorylated form of SGK preceded the increase in Na+ transport, and specific inhibition of PI3K inhibited both phosphorylation of SGK and mineralocorticoid-induced Na+ transport. Insulin both augmented SGK phosphorylation and synergized with mineralocorticoids in stimulating Na+ transport. In a Xenopus laevis oocyte coexpression assay, SGK-stimulated ENaC activity was also markedly reduced by PI3K inhibition. Finally, in vitro-translated SGK specifically interacted with the ENaC subunits expressed in Escherichia coli as glutathione S-transferase fusion proteins. These data suggest that SGK is a PI3K-dependent integrator of insulin and mineralocorticoid actions that interacts with ENaC subunits to control Na+ entry into kidney collecting duct cells.

Animals↗
PubMed1998

Microvascular tissue transfer in a pregnant patient.

Pregnancy is a relative contraindication for elective surgery. The primary concerns are for the safety of the fetus and the mother. However, there are particular problems involving microvascular surgery due to the pregnancy-associated hypercoagulable state. The authors were presented with a 35-year woman, 20 weeks pregnant, with a degloved foot and ankle associated with an open distal tibia/fibula fracture (Gustilo IIIB). Salvage of her leg required a microvascular tissue transfer. Accordingly, a combined latissimus dorsi-serratus anterior free flap was performed with a saphenous vein graft to the popliteal vessels. The patient was hypercoagulable and there were extensive platelet clots. Her consumption of heparin was enormous. Postoperatively, she was treated with intravenous dextran for 5 days and for 17 days with intravenous heparin. After discharge, she was placed on subcutaneous heparin until she delivered a healthy baby. The flap survived and her leg was salvaged. The hypercoagulable state of pregnancy, as well as thromboprophylaxis, are discussed.

Adult↗
PubMed1998

The synergistic activity of alphavbeta3 integrin and PDGF receptor increases cell migration.

Integrins and growth factor receptors act synergistically to modulate cellular functions. The alphavbeta3 integrin and the platelet-derived growth factor receptor have both been shown to play a positive role in cell migration. We show here that a platelet derived growth factor-BB gradient stimulated migration of rat microvascular endothelial cells on vitronectin (9.2-fold increase compared to resting cells) in a alphavbeta3 and RGD-dependent manner. In contrast, this response was not observed on a beta1 integrin ligand, laminin; background levels of migration, in response to a platelet derived growth factor-BB gradient, were observed on this substrate or on bovine serum albumin (2.4- or 2.0-fold, respectively). Comparable results were obtained using NIH-3T3 cells. Platelet derived growth factor-BB did not change the cells' ability to adhere to vitronectin, nor did it stimulate a further increase in proliferation on vitronectin versus laminin. In addition, platelet derived growth factor-BB stimulation of NIH-3T3 cells did not alter the ability of alphavbeta3 to bind RGD immobilized on Sepharose. The alphavbeta3 integrin and the platelet derived growth factor receptor-beta associate in both microvascular endothelial cells and NIH-3T3 cells, since they coprecipitated using two different antibodies to either alphavbeta3 or to the platelet derived growth factor receptor-beta. In contrast, beta1 integrins did not coprecipitate with the platelet derived growth factor receptor-beta. These results point to a novel pathway, mediated by the synergistic activity of alphavbeta3 and the platelet derived growth factor receptor-beta, that regulates cell migration and, therefore, might play a role during neovessel formation and tissue infiltration.

3T3 Cells↗
PubMed1995

Posterior intermalleolar ligament of the ankle: normal anatomy and MR imaging features.

OBJECTIVE: The purposes of this study were to delineate the normal anatomy and MR imaging features of the posterior intermalleolar ligament--a normal ligamentous variant of the posterior portion of the ankle--and to identify normal anatomic characteristics that may account for the role of the ligament in the development of posterior impingement syndrome. MATERIALS AND METHODS: The prevalence, size, and shape of the posterior intermalleolar ligament were documented in 36 cadaveric ankles and in 97 MR studies of the ankle in patients with and without symptoms. RESULTS: The posterior intermalleolar ligament was identified in 20 (56%) of the 36 cadaveric feet. It was 1-8 mm wide, and its diameter (anterior to posterior) was 5-8 mm. The ligament often resembled a meniscus, and in one case its anterior lip herniated into the ankle joint. The posterior intermalleolar ligament was detected in 18 (19%) of the 97 MR studies of the ankle. It was visualized on coronal T1- or T2-weighted images as a distinct, hypointense band traversing between the posterior talofibular ligament and the inferior transverse ligament. CONCLUSION: The posterior intermalleolar ligament is a normal variant of the posterior ligaments of the ankle and is present in a significant number of persons. It is best seen on coronal T1- and T2-weighted MR images. Its meniscuslike shape and occasional extension into the ankle joint may account for the development of posterior impingement syndrome in susceptible persons.

Adolescent↗
PubMed1987

Hormone-induced and maturational changes in electric organ discharges and electroreceptor tuning in the weakly electric fish Apteronotus.

Plasticity in the frequency of the electric organ discharge (EOD) and electroreceptor tuning of weakly electric fish was studied in the genus Apteronotus. Both hormone-induced and maturational changes in EOD frequency and electroreceptor tuning were examined. Apteronotus is different from all other steroid-responsive weakly electric fish in that estradiol-17 beta, rather than androgens, induces discharge frequency decreases. This result can account for the 'reversed' discharge frequency dimorphism found in Apteronotus in which, counter to all other known sexually dimorphic electric fish, females have lower discharge frequencies than males. Studies of electroreceptor tuning in Apteronotus indicate that electroreceptors are closely tuned to the frequency of the EOD. This finding was noted not only in adult animals, but also in juvenile animals shortly after the onset of their EODs. Tuning plasticity in Apteronotus, as in other species studied, is associated with altered EOD frequencies and was noted in both maturational EOD changes and in estrogen-induced changes. Thus, tuning plasticity appears to be a general phenomenon which occurs concurrent with a variety of EOD changes.

Androgens↗
PubMed1979

Fetal-maternal transfusion following early abortion.

Therapeutic abortion has been a major potential source of Rh isoimmunization. Popularization of early termination necessitates reconfirmation of established policies. This study involved 75 patients, selected at random, in whom pre- and post-abortion blood smears were studied for fetal-maternal hemorrhage. Results showed that this may occur even in early suction termination. The significance of these findings was discussed in relation to the cost-effectiveness and the dosage of anti-Rho (D) globulin administered to patients.

Abortion, Therapeutic↗
PubMed1977

Temperature regulation in a hypometabolic primate, the slow loris (Nycticebus coucang).

Six slow loris were exposed to air temperatures between 10 degrees C and 40 degrees C. Rectal temperature was stable (mean, 34.8 degrees C) at air temperatures between 17 degrees C and 31 degrees C; at higher air temperatures, the animals became hyperthermic. Oxygen consumption was minimal at air temperatures of 31.4-36.6 degrees C; the mean value (0.250 ml O2 g-1 h-1) was only 36% of the expected level for a eutherian Mammal. The slow loris increased its heat production at lower air temperatures. Thermal polypnea occurred in response to heat, and some of the animals were able to dissipate their entire metabolic heat production at lower air temperatures. Thermal polypnea occurred in response to heat, and some of the animals were able the combined thermal conductance of the tissues and haircoat was 73% of the predicted values. It was concluded that, in spite of its low metabolic rate, the slow loris had effective responses to moderate cold, and that, in addition, it was well adapted to a hot climate.

Animals↗
PubMedDate not supplied

Osmotic load from glucose polymers.

Glucose polymer is a carbohydrate source with variable chain lengths of glucose units which may result in variable osmolality. The osmolality of two commercial glucose polymers was measured in reconstituted powder infant formulas, and the change in osmolality of infant milk formulas at the same increases in energy density (67 kcal/dL to 81 and 97 kcal/dL) from the use of additional milk powder or glucose polymers was compared. All samples were prepared from powders (to nearest 0.1 mg), and osmolality was measured by freezing point depression. For both glucose polymers the within-batch variability of the measured osmolality was less than 3.5%, and between-batch variability of the measured osmolality was less than 9.6%. The measured osmolality varies linearly with energy density (p less than 0.001) and was highest in infant formula reconstituted from milk powder alone. However, there exist significant differences in the measured osmolality between different glucose polymer preparations. At high energy densities (greater than or equal to 97 kcal/dL), infant milk formulas prepared with milk powder alone or with the addition of certain glucose polymer preparation may have high osmolality (greater than or equal to 450 mosm/kg) and theoretically predispose the infant to complications of hyperosmotic feeds.

Glucose↗