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T Vu

Publications and source records attributed to T Vu.

51 records · Page 3Linked to original sources

Regulation of neutrophil interleukin 8 gene expression and protein secretion by LPS, TNF-alpha, and IL-1 beta.

Neutrophils are possibly involved in the pathogenesis of various lung diseases through the release of numerous mediators. In the present study, we studied the regulation of IL-8 gene induction and protein secretion in human blood neutrophils. Northern blot analysis revealed that LPS increased IL-8 mRNA levels in neutrophils, with a maximal fivefold increase by 2 h. IL-8 mRNa levels returned to baseline values within 12 h. In contrast, LPS-stimulated monocytes demonstrated a sustained increase of IL-8 mRNA levels for more than 24 h. TNF-alpha, IL-1 beta, and phorbol myristate acetate also increased IL-8 mRNA levels in neutrophils. Immunohistochemical analysis confirmed that IL-8 was localized within stimulated neutrophils. IL-8 secretion by neutrophils and monocytes was quantified using a specific ELISA for IL-8. Resting neutrophils secreted minimal IL-8 activity. However when cells were stimulated with LPS, TNF-alpha, or IL-1B, neutrophils secreted IL-8. IL-8 secretion was most marked during the first 2 h after stimulation and decreased thereafter. In contrast, monocytes maintained a high rate of IL-8 secretion over 12 h. Although a single monocyte secreted 70-fold more IL-8 than did a single neutrophil after 4 h of incubation, the high abundance of neutrophils in peripheral blood made the neutrophil-secreted IL-8 more significant. During the first 2 h, neutrophils secreted approximately 40% of the IL-8 released by monocytes in the same volume of blood. This ratio decreased to 9% after 12 h. Neutrophil-secreted IL-8 may play an autocrine or paracrine role during the initial stage of inflammation.

Cells, Cultured↗

Interleukin 4 prevents the induction of tissue factor mRNA in human monocytes in response to LPS or PMA stimulation.

Increased expression of tissue factor (TF) procoagulant activity by blood monocytes and tissue macrophages is implicated in a number of thrombotic disorders, as well as in fibrin deposition associated with inflammatory lesions and immunological diseases. We found that interleukin 4 (IL-4), a T lymphocyte-derived cytokine known to regulate a number of monocyte functions, inhibited the production of TF by monocytes in response to endotoxin and phorbol myristate acetate (PMA) in vitro. IL-4 had a concentration-dependent inhibitory effect on functional TF procoagulant activity (PCA) and reduced the binding of an anti-TF antibody, as assessed by flow cytometry analysis. Moreover, IL-4 reduced LPS- and PMA-induced TF mRNA levels. TF mRNA stability was not modified by IL-4 after the arrest of transcription by actinomycin D. We thus conclude that mRNA suppression is mediated by an effect occurring at the transcriptional level. Our results also show that the suppressive effect of IL-4 is independent of an increase in the intracellular concentration of cyclic AMP, another established inhibitor of TF production. Locally produced IL-4 might thus contribute to limiting the consequences of monocyte activation.

Blood Coagulation↗

Expression of AMPA-selective glutamate receptor subunits in morphologically defined neurons of the mammalian cochlear nucleus.

Glutamate and related amino acids mediate fast excitatory neurotransmission in the vertebrate CNS via ligand-gated cationic channels in the neuronal membrane. These channels are composed of different subunits that assemble into a functional receptor/channel complex. Although studies have shown that these subunits are differentially expressed in neurons, few studies have quantitatively addressed the cell-specific expression of glutamate subunits in relation to known glutamatergic pathways. In the vertebrate auditory system, glutamate is the proposed neurotransmitter of the auditory nerve and parallel fiber pathways. In situ hybridization histochemistry was used to localize AMPA-selective glutamate receptor subunit mRNAs in seven cell types of the rat cochlear nucleus. GluR1-GluR4 AMPA-selective subunits were all expressed in cochlear nucleus neurons; however, the subunits expressed in identified cells varied with the cell type. Granule cells, previously not known to receive glutamatergic input, expressed GluR2 and GluR4 subunits. Cartwheel and stellate interneurons in the dorsal cochlear nucleus, which receive parallel fiber input, expressed all four subunits. Neurons receiving synaptic input from the auditory nerve, including globular, round, spherical, and fusiform cells, expressed GluR2, GluR3, and GluR4 subunits. Furthermore, a subpopulation of round cells in the ventral cochlear nucleus, and fusiform cells in the dorsal cochlear nucleus, expressed the GluR3 subunit at greatly reduced levels compared to neighboring cells. The results confirm the auditory nerve and parallel fiber pathways as glutamatergic and identify a third synaptic population, projecting to granule cells, which is likely glutamatergic. The data suggest that the composition of GluR1-GluR4 subunits on neurons in the cochlear nucleus may be related to presynaptic input; moreover, heterogeneous patterns of expression of the GluR3 subunit, in addition, suggest that variability in mRNA levels within one population of morphologically defined cells is present.

Animals↗

Neurons in the rat medulla oblongata containing neuropeptide Y-, angiotensin II-, or galanin-like immunoreactivity project to the parabrachial nucleus.

Projections from the medulla to the parabrachial complex of the rat were examined for their content of neuropeptide Y-, angiotensin II- or galanin-like immunoreactivity using combined retrograde tracing and immunohistochemical techniques. Rhodamine-labelled latex microspheres were stereotaxically injected into discrete nuclei of the parabrachial complex. After survival of two to five days, colchicine (100 micrograms in 10 microliters saline) was injected into the cisterna magna. One day later, rats were perfused and the brainstems were prepared for visualization of the retrograde tracer and immunoreactivity of one of the three peptides. Retrograde labelling verified that the area postrema, nucleus of the tractus solitarius, caudal spinal nucleus of the trigeminal nerve, parvocellular reticular nucleus, and ventrolateral medulla including the rostral ventrolateral medulla and nucleus paragigantocellularis project to the lateral parabrachial and Kölliker-Fuse nuclei. While most projections were primarily ipsilateral, a small proportion of the projections from the ventrolateral medulla was bilateral. Neurons containing neuropeptide Y-like immunoreactivity were found in the caudal and intermediate nucleus of the tractus solitarius, dorsal to the lateral reticular nucleus and in the nucleus paragigantocellularis. After bilateral microsphere injections into the lateral parabrachial and Kölliker-Fuse nuclei, double-labelled neurons were found dorsal to the lateral reticular nucleus of caudal and intermediate medullary levels, at the ventral surface of the medulla at intermediate levels and in the nucleus paragigantocellularis at rostral levels. Neurons with angiotensin II-like immunoreactivity were observed at the dorsomedial border of the caudal and intermediate nucleus of the tractus solitarius, in the area postrema and in the lateral reticular nucleus and nucleus paragigantocellularis. Of these neurons, small numbers in the nucleus of the tractus solitarius and ventrolateral medulla also projected to the lateral parabrachial and Kölliker-Fuse nuclei. Neurons containing galanin-like immunoreactivity were found in the caudal nucleus of the tractus solitarius, the area postrema, the spinal trigeminal nucleus, the raphe nuclei (pallidus and obscurus), the nucleus paragigantocellularis and dorsal to the lateral reticular nucleus. Of these cells, double-labelled neurons were found in the commissural and medial subdivisions of the caudal nucleus of the tractus solitarius and in the rostral ventrolateral medulla including the ventral surface and the nucleus paragigantocellularis. The results suggest that neuropeptide Y, angiotensin II and galanin may serve as neurochemical messengers in pathways from the medulla to the parabrachial complex. The location of double-labelled neurons suggests that the information relayed by these neurons is related to autonomic activity.

Angiotensin II↗

Endothelial cells enhance spontaneous metastasis of human lung carcinoma cells in athymic mice.

The process of adhesion to endothelial cells is an important step in the progression to metastatic disease. The use of human neoplastic cell lines (now increasingly used in the study of the mechanisms of metastasis) in studying interactions with normal endothelial cells is therefore pertinent. In this report, the enhanced ability of a metastatic variant, MV522, of a human lung carcinoma cell line to adhere to endothelial cell monolayers is demonstrated. The ability to spontaneously metastasize from subcutaneous sites in athymic mice, of in vitro selected endothelial adhesive subpopulations of MV522 is also shown.

Animals↗

The scalp as a donor site: revisited.

The scalp cannot be used as skin graft donor site with impunity. A review of 2,620 charts identified 194 pediatric patients whose scalps served as donor sites for split-thickness skin grafts for the treatment of acute burns. The overall incidence of alopecia was 32%. However, the incidence of alopecia in unburned scalps was 13%. The occurrence of alopecia in this group was associated with larger burn area requiring more frequent use of the scalp and shorter intervals between graft harvests (p less than 0.05). Among this group of patients (n = 15), nine had mild spotty alopecia, four had surgically correctable alopecia, and two had global patchy alopecia not amenable to surgical correction. In the patients with concomitant burns to their scalps, the incidence of alopecia was 61%. Whether the burn or the graft harvest caused alopecia could not be established. Meticulous donor site care is mandatory in this latter group when the scalp donor site is indicated.

Adolescent↗

Divergent ontogeny of sigma and phencyclidine binding sites in the rat brain.

The postnatal developmental patterns of sigma (sigma) and phencyclidine (PCP) binding sites were compared in the rat brain. The results show diametrically different ontogenic patterns for the sites. While both the affinity and the density of sigma sites remain constant throughout the developmental period tested (postnatal day 1 to 1 year), the density of PCP binding sites increases from the time of birth, reaching the adult level by postnatal day 14. The differences in developmental patterns provide evidence for distinctive properties of cerebral sigma and PCP binding sites.

Aging↗

Correlation between bleeding times and platelet counts in women with preeclampsia undergoing cesarean section.

Platelet count and bleeding time and the correlation between these two variables in women with preeclampsia who received epidural or general anesthesia for cesarean section were evaluated. The study included 106 women with preeclampsia who were undergoing cesarean section and 94 healthy, term parturients receiving epidural anesthesia for labor analgesia or for cesarean section. Platelet counts were measured using an automated Coulter Counter, and bleeding times were measured using the modified Ivy bleeding time technique. Platelet count was significantly lower and bleeding time significantly prolonged in patients with preeclampsia compared with the control group (P less than 0.0001). In the preeclampsia group, eight patients (7.5%) had thrombocytopenia (platelet count less than 100,000/mm3), whereas in the control group, all women had a normal platelet count (greater than 150,000/mm3). All but one patient with thrombocytopenia had prolonged bleeding time. In addition, 34% of those women with severe preeclampsia and 13% with mild preeclampsia had prolonged bleeding time, although their platelet count was adequate. In the control group, 2% had abnormal bleeding time in the presence of a normal platelet count. There was good correlation between bleeding time and platelet count only when platelet count was lower than 100,000/mm3 (r = -0.76, P less than -0.02).

Adult↗

Synthesis and pharmacological evaluation of 5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptane derivatives.

1 alpha,2 beta(5Z),3 beta(1E,3S),4 alpha,5 alpha,6 alpha]-7-[5,6-Epoxy-3- (3-cyclohexyl-3-hydroxy-3-methyl-1-propenyl)-7-oxabicyclo[2.2.1]-hept-2- yl]-5-heptenoic acid (31) and [1 alpha,2 beta(5Z),3 beta(1E,3S),4 alpha,5 alpha,6 alpha]-7-[5,6-epoxy-3-[3-hydroxy-5-(p-hydroxyphenyl)-1- pentenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (37) were found to be selective TxA2 antagonists at the platelet and pulmonary thromboxane receptors. An efficient stereospecific synthesis of these compounds and a series of structural analogues is described. Compounds 31 and 37 both inhibited the bronchoconstriction induced by arachidonic acid in the anesthetized guinea pig.

Adenosine Diphosphate↗

Conformationally restricted mimics of vitamin D rotamers.

Drug developments in the vitamin D field have continued to focus on structure-function studies of analogs produced by chemically modifying the structure of 1alpha,25-dihydroxyvitamin D(3) (1,25-D3) and its metabolites. Direct structural information gleaned from X-ray crystallographic or NMR studies regarding the ligand-receptor complex and other guest-host systems, which are likely involved in initiating biologic responses, also offers potential insight into drug design. Evidence has accrued suggesting that topologically different conformers of 1,25-D3 may bind to proteins in different ways, including the induction of different conformations of protein. This paper concerns our progress on the chemical synthesis of analogs (e.g. ansa-steroids, suprasterols, vinylallenes and other analogs) conformationally locked or at least rotationally restricted to mimic higher energy conformers of 1,25-D3.

Animals↗

Mobile and portable dentistry: alternative treatment services for the elderly.

With the rapidly expanding geriatric population in the United States, the demand for geriatric dentistry is rising. With the financial, transportation, and motivational barriers the geriatric population faces, it can be difficult for them to seek dental treatment in a traditional setting. Mobile and portable dental units can be used as alternative methods to provide dental care to the geriatric population. Mobile and portable dental units offer advantages such as providing community outreach, increasing personal satisfaction for geriatric clients and dental professionals, and providing dental care to those who would otherwise not receive treatment due to some of the barriers. Although mobile and portable dental units are ideal for long-term facilities, disadvantages do exist in implementing the use of these systems. These include the initial cost of implementing such a unit, limitation of treatment options, the number of clients seen in a day, and maintenance for the unit. Until more research can be done to find ways to improve the quality of dental care for the geriatric population, these units seem to be a reasonable alternative to the traditional approach to providing the elderly with the dental care they require.

Aged↗

Time-dependent effects of intermittent hydrostatic pressure on articular chondrocyte type II collagen and aggrecan mRNA expression.

The normal loading of joints during daily activities causes the articular cartilage to be exposed to high levels of intermittent hydrostatic pressure. This study quantified effects of intermittent hydrostatic pressure on expression of mRNA for important extracellular matrix constituents. Normal adult bovine articular chondrocytes were isolated and tested in primary culture, either as high-density monolayers or formed aggregates. Loaded cells were exposed to 10 MPa of intermittent hydrostatic pressure at a frequency of 1 Hz for periods of 2, 4, 8, 12, and 24 hrs. Other cells were intermittently loaded for a period of 4 hrs per day for 4 days. Semiquantitative reverse transcription polymerase chain reaction assays were used to assess mRNA signal levels for collagen types II and I and aggrecan. The results showed that type II collagen mRNA signal levels exhibited a biphasic pattern, with an initial increase of approximately five-fold at 4 and 8 hrs that subsequently decreased by 24 hrs. In contrast, aggrecan mRNA signal increased progressively up to three-fold throughout the loading period. Changing the loading profile to 4 hrs per day for 4 days increased the mRNA signal levels for type II collagen nine-fold and for aggrecan twenty-fold when compared to unloaded cultures. These data suggest that specific mechanical loading protocols may be required to optimally promote repair and regeneration of diseased joints.

Aggrecans↗