Search PubMed⌕ Search

Biomedical subjects

T Lee

Publications and source records attributed to T Lee.

At least 181 records · Page 10Linked to original sources

Regulated Breathless receptor tyrosine kinase activity required to pattern cell migration and branching in the Drosophila tracheal system.

Receptor tyrosine kinases (RTKs) are members of a diverse class of signaling molecules well known for their roles in cell fate specification, cell differentiation, and oncogenic transformation. Recently several RTKs have been implicated in cell and axon motility, and RTKs are known to mediate chemotactic guidance of tissue culture cells. We have investigated whether the Drosophila FGF receptor homolog, Breathless (BTL), whose activity is necessary for each phase of branching morphogenesis in the embryonic tracheal system, might play a role in guiding the directed migration of tracheal cells. We found that expression of a constitutively active receptor during tracheal development interfered with directed tracheal cell migration and led to extra secondary and terminal branch-forming cells. Reduction in endogenous BTL signaling enhanced the cell migration defects while suppressing the ectopic branching defects. These results are consistent with a model for tracheal development in which spatially regulated BTL activity guides tracheal cell migration and quantitatively regulated BTL activity determines the patterns of secondary and terminal branching cell fates.

Animals↗

Increased iron in the substantia nigra of 6-OHDA induced parkinsonian rats: a nuclear microscopy study.

The trace elemental concentrations, including iron, in the substantia nigra (SN) of a 6-OHDA induced rat model of Parkinson's disease were measured using nuclear microscopy. Only rats that exhibited amphetamine induced rotation of more than 7 turns/min were used. The results showed that the iron levels were significantly increased in the 6-OHDA lesioned SN, compared with the intact contralateral SN, and the SN of normal control rats injected with ascorbic acid, which showed no significant difference in iron levels between injected and non-injected sides. In both 6-OHDA lesioned and ascorbic acid injected SN, there were no alterations in the levels of calcium, magnesium, copper and zinc. In the 6-OHDA lesioned SN there was an almost complete loss of tyrosine hydroxylase positive cells in the SN. These results suggested that the 6-OHDA induced dopaminergic cell death may be related to the increased iron.

Animals↗

Role of protein kinase C-beta isozyme in activation of latent human immunodeficiency virus type 1 in promonocytic U1 cells by phorbol-12-myristate acetate.

Protein kinase C (PKC) appears to play a role in replication of human immunodeficiency virus type 1 (HIV-1). PKC is a family of at least 12 isozymes. In this study, we investigated a role of Ca(2+)-dependent PKC isozymes (alpha, beta, and gamma) in activation of latent HIV-1 in U1, a chronically infected promonocytic cell line, using polyclonal rabbit anti-PKC isozyme antibodies as specific inhibitors. Antibodies were introduced intracellularly by electroporation and then cells were stimulated with PMA. HIV-1 production was measured as p24 antigen using ELISA and reverse transcriptase activity. Anti-PKC beta antibody significantly inhibited PMA-induced HIV-1 production, whereas antibodies against PKC alpha and gamma had no significant effect. Furthermore, anti-PKC beta antibody inhibited PMA-induced activation of NF-kappa B and HIV-1 LTR. Preincubation of anti-PKC beta antibody with its antigenic peptide reversed the inhibitory effect of anti-PKC beta antibody. This study suggest that PKC beta plays a role in PMA-induced activation of latent HIV-1.

Animals↗

Photolyase of Myxococcus xanthus, a Gram-negative eubacterium, is more similar to photolyases found in Archaea and "higher" eukaryotes than to photolyases of other eubacteria.

We report the identification of the gene encoding a DNA photolyase (phrA) from the Gram-negative eubacterium Myxococcus xanthus. The deduced amino acid sequence of M. xanthus photolyase indicates that the protein contains 401 amino acids (Mr 45,071). By comparison of the amino acid and DNA sequences with those of other known photolyases, it has been found that it is more similar to the deduced amino acid sequences of the photolyases of "higher" eukaryotes than to the photolyases of other eubacteria. Recombinant plasmids carrying M. xanthus phrA rescue the photoreactivation activity of an irradiated strain of Escherichia coli with a deletion in phrA. This rescue is light-dependent.

Amino Acid Sequence↗

Dust: a diagnostic of the hydrologic cycle during the last glacial maximum.

Dust concentrations in ice of the last glacial maximum (LGM) are high in ice cores from Greenland and Antarctica. The magnitude of the enhancements can be explained if the strength of the hydrologic cycle during the LGM was about half of that at present. This notion is consistent with a large decrease (5 degrees Celsius) in ocean temperature during the LGM, as recently deduced from measurements of strontium and calcium in corals.

Antarctic Regions↗

Antenna to leg transformation: dynamics of developmental competence.

We explore the transformation of antenna to leg in Drosophila melanogaster, using ectopically expressed transgenes with heat shock promoters: heat shock Antennapedia, heat shock Ultrabithorax, and heat shock mouse Hox A5. We determined the frequency of transformation of several leg markers in response to Antennapedia protein delivered by heat shock at different times and doses. We also studied stage-specific responses to the transgene, heat shock mouse Hox A5. Results show that each marker has its own stage and dose-specific pattern of response. The same marker could pass through a period of high-dose inhibition followed by a dose-independent response and then a positive dose-dependent phase. The heat shock-induced transgenes and spineless aristapedia transformed the apterous enhancer trap antenna disc expression pattern toward the pattern found in leg discs. These results are considered in relation to developmental competence-the ability of developing tissue to respond to internal or external influences. The results suggest that all genes tested interact with the same competence system and that at least two classes of mechanisms are associated with antenna to leg transformation: one comprises global mechanisms that permit transformation over approximately 24 hr; the second class of mechanisms act very locally and are responsible for changes in dose response on the order of 4-8 hr.

Animals↗

Acetylation of sphingosine by PAF-dependent transacetylase.

Sphingosine induces many protein kinase C-dependent and -independent effects on biological systems. In parallel, C2-ceramide used by investigators as an unnatural, cell permeable analog of long-chain acyl-ceramides, possesses biological activities similar with natural ceramides. We have recently characterized a membrane-associated. CoA-independent transacetylase that can transfer the acetate group from PAF to sphingosine and form C2-ceramide. This enzyme has a strict stereochemical configuration requirement for sphingosine; only the naturally-occurring D-erythro-isomers of sphingosine accepts the acetate from PAF. Also, it has a rigid substrate specificity for sphingolipid-related analogues. Dipalmitoyl-glycerophosphocholine (-GPC) or hexadecylarachidonoyl-GPC can not transfer their long-chain acyl groups directly to sphingosine and sphingosine can not be acetylated by acetyl-CoA:lyso-PAF acetyltransferase. Results obtained from studies on pH optima, subcellular distribution, temperature sensitivities, inhibitors, tissue distributions, and expression of enzyme activities in Xenopus oocytes suggest that PAF:sphingosine transacetylase is similar, but not identical to the PAF:lysophospholipid transacetylase we have previously identified. The transacetylases function to diversify the biological responses of PAF.

Acetylation↗

Prevalence of vertebral fractures in chinese men and women in urban Taiwanese communities.

Reports on the prevalence (or incidence) rates of vertebral fracture have been available, but they are limited concerning non-white populations and men of all races. This study used the radiomorphometric method to survey the prevalence rate of vertebral fracture for ethnic Chinese women 40 years and older and Chinese men 65 and older who were randomly selected from four major cities in Taiwan. Three sets of reference values of the height ratios were used for middle-aged women, elderly women, and elderly men. The results showed that in Chinese women, the prevalence rate of vertebral fracture was low before age 50 and showed a steady increase thereafter. In men, the increase was small until age 80. The overall adjusted prevalence rate of vertebral fracture for women older than 65 was 20% and that for men, 12.5% (95% confidence interval 18-22% and 11-14%, respectively.) If only severe deformity was counted [height ratio lower than normal mean minus 4 standard deviations (SD), or Grade II deformity], the adjusted prevalence rate was 15.5% for elderly women and 9.5% for elderly men (95% confidence interval 14-17%, and 8-11%, respectively.) The overall adjusted prevalence rate for women aged 40 and over was 6.8% (95% confidence interval 5.7-8%), or 4.5% (95% confidence interval 3.6-5. 5%) for Grade II lesions. Moreover, for subjects with fracture, elderly women tended to have more fractured vertebrae per person and more Grade II fractures than elderly men. Thus, Chinese women residing in cities of Taiwan had a relatively high prevalence rate of vertebral fracture, a finding compatible with that for United States or European white women, or for Japanese women residing in America. Elderly Chinese men also have a high prevalence rate of vertebral fracture. The age-specific female-to-male ratio of prevalence rate was about 1.5 to 2.3 between age 65 and 80, and close to unity after age 80.

Adult↗

Improved retrograde axonal transport and subsequent visualization of tetramethylrhodamine (TMR) -dextran amine by means of an acidic injection vehicle and antibodies against TMR.

We studied the ability of various dextran amines (DA) to retrogradely label cortical neurons to the full extent of their dendritic configurations. Corticothalamic neurons were labeled by pressure injection of DA into the ventrobasal thalamic nuclei of the rat brain. Of fluorescein-, Texas Red-, Cascade Blue- and tetramethylrhodamine (TMR)-DAs of MW 3000 and TMR-DA of MW 10,000, neurons were most efficiently labeled with TMR-DA of MW 3000. The use of acidic vehicles (pH 1-3) for dissolving TMR-DA enhanced the retrograde labeling, as compared with that of a neutral vehicle. The retrograde labeling with TMR-DA was more clearly demonstrated by using anti-TMR antibodies; the indirect immunofluorescence method with a rhodamine-conjugated secondary antibody and immunoperoxidase method with a peroxidase anti-peroxidase (PAP) complex revealed that the dendrites of many corticothalamic neurons were filled with TMR-DA. The Golgi-like retrograde labeling of TMR-DA visualized by the PAP immunoperoxidase method was comparable with that of biotinylated DA by the avidin-biotinylated peroxidase complex method. Similar Golgi-like dendritic staining was observed among corticospinal neurons after injection of TMR-DA into the corticospinal tract of the spinal cord. Most apical dendrites of corticospinal neurons extended into layer I, whereas those of corticothalamic neurons ended in layer IV or the deep part of layer III. The TMR-DA injection under acidic conditions and immunostaining with the anti-TMR antibodies are considered to be a useful method to visualize the dendrite configuration of cortical projection neurons.

Animals↗

The effect of variable size posterior wall acetabular fractures on contact characteristics of the hip joint.

The indications for open reduction and internal fixation of posterior wall acetabular fractures associated with a clinically stable hip joint are unclear. In previous work a large posterior wall defect (27% articular surface area) resulted in significant alteration of load transmission across the hip; specifically, there was a transition from evenly distributed loading along the acetabular articular surface to loading concentrated mainly in the superior portion of the articular surface during simulated single leg stance. However, the majority of posterior wall fractures involve a smaller amount of the articular surface. Posterior wall acetabular fractures not associated with instability of the hip are commonly treated nonoperatively. This practice does not account for the size of the posterior wall fracture. To study the biomechanical consequences of variably sized articular defects, a laboratory experiment was conducted evaluating three progressively larger posterior wall defects of the acetabulum during simulated single leg stance using superlow Fuji prescale film (Itochu International, New York): (a) 1/3 articular surface width through a 50 degrees arc along the posterior wall of the acetabulum, (b) 2/3, and (c) 3/3 articular width defects through the same 50 degrees arc along the posterior wall of the acetabulum. In the intact acetabulum, 48% of the total articular contact was located in the superior acetabulum. Twenty-eight percent of articular contact was in the anterior wall region of the acetabulum and 24% in the posterior wall region. After the 1/3 width posterior wall defect, 64% of the articular contact was located in the superior acetabulum (p = 0.0011). The 2/3 width posterior wall defect resulted in 71% of articular contact area being located in the superior acetabulum (p = 0.0006). After the 3/3 width posterior wall defect, 77% of articular contact was located in the superior acetabulum, significantly greater than the intact condition (p < 0.0001) and 1/3 width defect (p = 0.0222). The total absolute contact areas for all defect conditions were significantly less than the intact conditions. The results of this study reconfirm the observation that posterior wall fractures of the acetabulum significantly alter the articular contact characteristics in the hip during single leg stance. The relationship between defect size and changes in joint contact showed that the smallest defect resulted in the greatest alteration in joint contact areas, whereas larger defects resulted in minor increments of change in contact area. This finding is of concern because the clinical practice of managing acetabular fractures nonoperatively if the hip joint is stable is based on the supposition that the joint retains enough integrity to function without undue risk of late posttraumatic osteoarthritis. A better understanding of the natural history of stable posterior wall acetabular fractures is needed to ascertain whether some of these fractures merit operative repair.

Acetabulum↗

Quality assessment issues of new immunosuppressive drugs and experimental experience.

There are established quality assessment schemes for the two immunosuppressive drugs that have entered routine clinical use: cyclosporine and tacrolimus. These two drugs, together with sirolimus and mycophenolic acid, have been the subject of recent consensus panel reports that have reached broad agreement on several issues relating to therapeutic monitoring of these agents. While the current quality assessment schemes are not based on validated reference methods, the data they yield on comparative assay performance are of value as a guide to patient management and for clinical studies of drug efficacy.

Cyclosporine↗