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Biomedical subjects

Y Lin

Publications and source records attributed to Y Lin.

At least 91 records · Page 5Linked to original sources

Embryonic control of epidermal cell patterning in the root and hypocotyl of Arabidopsis.

A position-dependent pattern of epidermal cell types is produced during the development of the Arabidopsis seedling root and hypocotyl. To understand the origin and regulation of this patterning mechanism, we have examined the embryonic expression of the GLABRA2 (GL2) gene, which encodes a cell-type-specific transcription factor. Using in situ RNA hybridization and a sensitive GL2::GFP reporter, we discovered that a position-dependent pattern of GL2 expression is established within protodermal cells at the heart stage and is maintained throughout the remainder of embryogenesis. In addition, we show that an exceptional GL2 expression character and epidermal cell pattern arises during development of the root-hypocotyl junction, which represents an anatomical transition zone. Furthermore, we find that two of the genes regulating seedling epidermal patterning, TRANSPARENT TESTA GLABRA (TTG) and WEREWOLF (WER), also control the embryonic GL2 pattern, whereas the CAPRICE (CPC) and GL2 genes are not required to establish this pattern. These results indicate that position-dependent patterning of epidermal cell types begins at an early stage of embryogenesis, before formation of the apical meristems and shortly after the cellular anatomy of the protoderm and outer ground tissue layer is established. Thus, epidermal cell specification in the Arabidopsis seedling relies on the embryonic establishment of a patterning mechanism that is perpetuated postembryonically.

Arabidopsis↗

Induced repatterning of type XVIII collagen expression in ureter bud from kidney to lung type: association with sonic hedgehog and ectopic surfactant protein C.

Epithelial-mesenchymal tissue interactions regulate the formation of signaling centers that play a role in the coordination of organogenesis, but it is not clear how their activity leads to differences in organogenesis. We report that type XVIII collagen, which contains both a frizzled and an endostatin domain, is expressed throughout the respective epithelial bud at the initiation of lung and kidney organogenesis. It becomes localized to the epithelial tips in the lung during the early stages of epithelial branching, while its expression in the kidney is confined to the epithelial stalk region and is lost from the nearly formed ureter tips, thus displaying the reverse pattern to that in the lung. In recombinants, between ureter bud and lung mesenchyme, type XVIII collagen expression pattern in the ureter bud shifts from the kidney to the lung type, accompanied by a shift in sonic hedgehog expression in the epithelium. The lung mesenchyme is also sufficient to induce ectopic lung surfactant protein C expression in the ureter bud. Moreover, the shift in type XVIII collagen expression is associated with changes in ureter development, thus resembling aspects of early lung type epigenesis in the recombinants. Respecification of collagen is necessary for the repatterning process, as type XVIII collagen antibody blocking had no effect on ureter development in the intact kidney, whereas it reduced the number of epithelial tips in the lung and completely blocked ureter development with lung mesenchyme. Type XVIII collagen antibody blocking also led to a notable reduction in the expression of Wnt2, which is expressed in the lung mesenchyme but not in that of the kidney, suggesting a regulatory interaction between this collagen and Wnt2. Respecification also occurred in a chimeric organ containing the ureter bud and both kidney and lung mesenchymes, indicating that the epithelial tips can integrate the morphogenetic signals independently. A glial cell line-derived neurotrophic factor signal induces loss of type XVIII collagen from the ureter tips and renders the ureter bud competent for repatterning by lung mesenchyme-derived signals. Our data suggest that differential organ morphogenesis is regulated by an intra-organ patterning process that involves coordination between inductive signals and matrix molecules, such as type XVIII collagen.

Animals↗

The influence of chronic antihypertensive treatment on the central pressor response in SHR.

UNLABELLED: We examined the influence of chronic antihypertensive treatment on the central pressor response in SHR. Adult male SHR were divided into 5 groups, i.e., those receiving 1) enalapril (Enal: 25 mg/kg/day in drinking water, n=12); 2) losartan (Los: 40 mg/kg/day, n=11); 3) candesartan (Cand: 4 mg/kg/day, n=12); 4) hydralazine+hydrochlorothiazide (H&H: 50+7.5 mg/kg/day, n=9); 5) vehicle ( CONTROL: n=9). At 4 weeks of treatment, hypertonic saline (0.25, 0.5 M) was intracerebroventricularly (i.c.v.) injected into conscious rats. Plasma catecholamines were measured before and after i.c.v. injection. On completion of the experiment, heart weight was measured, and angiotensin-converting enzyme (ACE) activity of the cerebrum was determined. All antihypertensive drugs elicited comparable reductions in systolic blood pressure, while heart rate was significantly higher in the H&H group than in the other groups during treatment. Pressor response to i.c.v. hypertonic saline (0.5 M) was significantly smaller in the Enal (12 +/- 3 mmHg) and Cand (11 +/- 2 mmHg) groups than in the Los (22 +/- 2 mmHg), H&H (16 +/- 2 mmHg), and CONTROL (29 +/- 5 mmHg) groups. Plasma catecholamines did not differ among the groups. Heart weight was lowest in the Enal group, followed by the Los and Cand groups. ACE activity of the cerebrum was significantly decreased in the Enal group. The results suggest that chronic treatment with various antihypertensive drugs differentially alters the central pressor response in SHR, and enalapril and candesartan are effective in attenuating this response.

Angiotensin-Converting Enzyme Inhibitors↗

Enzyme kinetics of cytochrome P450-mediated reactions.

The most common drug-drug interactions may be understood in terms of alterations of metabolism, associated primarily with changes in the activity of cytochrome P450 (CYP) enzymes. Kinetic parameters such as Km, Vmax, Ki and Ka, which describe metabolism-based drug interactions, are usually determined by appropriate kinetic models and may be used to predict the pharmacokinetic consequences of exposure to one or multiple drugs. According to classic Michaelis-Menten (M-M) kinetics, one binding site models can be employed to simply interpret inhibition (pure competitive, non-competitive and uncompetitive) or activation of the enzyme. However, some cytochromes P450, in particular CYP3A4, exhibit unusual kinetic characteristics. In this instance, the changes in apparent kinetic constants in the presence of inhibitor or activator or second substrate do not obey the rules of M-M kinetics, and the resulting kinetics are not straightforward and hamper mechanistic interpretation of the interaction in question. These unusual kinetics include substrate activation (autoactivation), substrate inhibition, partial inhibition, activation, differential kinetics and others. To address this problem, several kinetic models can be proposed, based upon the assumption that multiple substrate binding sites exist at the active site of a particular P450, and the resulting kinetic constants are, therefore, solved to adequately describe the observed interaction between multiple drugs. The following is an overview of some cytochrome P450-mediated classic and atypical enzyme kinetics, and the associated kinetic models. Applications of these kinetic models can provide some new insights into the mechanism of P450-mediated drug-drug interactions.

Algorithms↗

Plasmablastic lymphoma of the lung: report of a unique case and review of the literature.

Non-Hodgkin lymphomas associated with acquired immunodeficiency syndrome are heterogeneous. Recently, a novel subtype of non-Hodgkin lymphoma occurring mostly in patients with acquired immunodeficiency syndrome has been described and designated as plasmablastic lymphoma. The histomorphologic and immunophenotypic findings of this distinct subtype of non-Hodgkin lymphoma have been characterized previously. Most patients present with oral cavity involvement. We report a case of plasmablastic lymphoma presenting as a lung tumor. To our knowledge, this is the first case report of this unusual subtype of diffuse large B-cell lymphoma in this location.

Acquired Immunodeficiency Syndrome↗

Substrate inhibition kinetics for cytochrome P450-catalyzed reactions.

Most cytochrome P450 (P450 or CYP)-catalyzed reactions are adequately described by classical Michaelis-Menten kinetic parameters (e.g., Km and Vmax), which are usually determined by a saturation profile of velocity of product formation versus substrate concentration. In turn, these parameters may be used to predict pharmacokinetics. However, some P450 enzymes exhibit atypical or non-Michaelis-Menten kinetics, due largely to substrate inhibition at higher concentrations of substrate. Although the mechanism of substrate inhibition is unknown, ignoring it and truncating the data can lead to erroneous estimates of kinetic parameters. In the present study, 13 P450 marker substrates were examined with 10 recombinant P450 proteins, and 6 were found, to varying degrees, to exhibit substrate inhibition. To understand the nature of the inhibition, a kinetic model was proposed (assuming that two binding sites exist on the enzyme) and used to fit the experimental data. The derived data indicated that 1) the K(I) values (substrate inhibition) were approximately 1.2- to 10-fold greater than the respective K(S) values; 2) both K(S) and K(I) values may be affected by the interaction of the two bound substrates within the enzyme, exhibited by a factor alpha (alpha = 5.1-23.3); and 3) enzyme activity was inhibited markedly (39-97%) at excess concentrations of the substrates (beta = 0.03-0.61). These findings suggest that substrates have access to both the inhibitory site and catalytic site simultaneously (K(I) > K(S)). Furthermore, the two sites, in the presence of substrate, can interact with each other. Therefore, the degree of inhibition of the enzyme is dependent on the concentration of the substrate (usually >K(I)) that sufficiently occupies the inhibitory site.

Antineoplastic Agents↗

[Toxic effects of Cu, Zn and Mn on the inhibition of Chlorella pyrenoidosa's growth].

A standard method of algal bioassay for evaluating the toxicity of toxic chemicals was applied in the study. It was found that safety concentrations of Cu, Zn and Mn for Chlorella pyrenoidosa's growth were 31.8 micrograms/L, 65.0 micrograms/L and 5.5 mg/L, and 96 h-EC50 were 67.3 micrograms/L, 473.0 micrograms/L and 17.0 mg/L, respectively. According to both safety concentration and 96 h-EC50, the toxic sequences of these metals from high to low on the inhibition of C. pyrenoidosa's growth were Cu, Zn and Mn. The different affinities between different metal ions and algal cells are mainly responsible for the different inhibitions of C. pyrenoidosa's growth.

Chlorella↗

[Treatment of dilute solution anilines-containing with displacement by extraction].

It was found that the biodegradability (indicated by BOD5/CODCr value of water solution containing anilire or chloroaniline declined with the increasing of their concentration. In order to bio-treat such water, decrease of the solute's concentration was necessary. Based on the research of organic solvents' and complexing agent's biodegradability, a series of extraction experiments were conducted for aniline and m-chloroaniline with complexing agent or physical solvent. The factors influencing the distribution ratio were discussed. The BOD5/CODCr value of raffinates showed that the raffinate can be treated by biological degradation without dilution if suitable solvent was choosed. It was proved that displacement by extraction had great potentiality for treating wastewater containing non-biodegradable organic contaminant.

Aniline Compounds↗

Dendritic growth induced by BMP-7 requires Smad1 and proteasome activity.

Bone morphogenetic proteins (BMPs) induce dendritic growth in cultured sympathetic neurons; however, the signaling pathways that mediate this dendrite-promoting activity have not been previously characterized. Here we report studies of the signaling events that regulate the growth of these afferent processes. We find that Smad1 is expressed in sympathetic neurons and that BMPs rapidly induce its phosphorylation and translocation from the cytoplasm to the nucleus. Furthermore, a dominant negative form of Smad1 inhibits BMP-7-induced dendritic growth, suggesting a requirement for Smad1 activation in this biological activity of BMP-7. A physical interaction between Smad1 and components involved in the proteasome-mediated degradation system was detected with a yeast two-hybrid screen, thereby prompting an examination of the effects of proteasome inhibitors on dendritic growth. Lactacystin and ALLN (N-acetyl-Leu-Leu-norleucinal) selectively blocked BMP-7-induced dendritic growth without adversely affecting either cell viability or axonal growth. Moreover, studies of transfected P19 cells suggest that the proteasome inhibitors directly block the effects of Smad1 on the transcriptional activity of the Tlx-2 promoter. These data indicate that BMP-induced dendritic growth requires Smad1 activation and involves proteasome-mediated degradation events.

Acetylcysteine↗

Testosterone, 7-benzyloxyquinoline, and 7-benzyloxy-4-trifluoromethyl-coumarin bind to different domains within the active site of cytochrome P450 3A4.

Testosterone, 7-benzyloxyquinoline, and 7-benzyloxy-4-trifluoromethyl-coumarin, marker substrates for cytochrome P450 3A4 are commonly used within the pharmaceutical industry to screen new chemical entities as inhibitors of CYP3A4 in a high-throughput manner to predict the potential for drug-drug interactions. However, it has been observed that inhibition data obtained with a given CYP3A4 probe substrate may not correlate well with results from a different probe. As a consequence, the choice of the probe compound becomes an important consideration in such screens. In the present study, kinetic interactions between either two of the above three substrates were evaluated, and three-dimensional nonlinear regression analysis was performed to understand the kinetic mechanisms of drug interaction. Our results demonstrate that the kinetic interaction between each pair of substrates does not appear to be competitive and that the interactions are characterized by an unchanged or a decrease in both apparent K(m) (a = 0.21-0.72, a change of K(m) in the absence of the effector) and V(max) (alpha and beta = 0.09-0.75, changes of V(max) in the absence of the effector). These data suggest that 1) the three substrates bind to different domains; 2) at least two substrates can coexist in the active site of CYP3A4; and 3) the two bound substrates interact kinetically with each other (e.g., through steric hindrance), thereby leading to a change in both apparent kinetic parameters and partial inhibition. Selection of multiple substrates, which are shown not to be competitive, is necessary to accurately predict CYP3A4 inhibition and the potential for drug-drug interaction.

Baculoviridae↗

Glucocorticoid receptor and heat shock protein 90 in peripheral blood mononuclear cells from asthmatics.

OBJECTIVE: To investigate the expression of glucocorticoid receptor (GR) and heat shock protein 90 (HSP90) mRNA in peripheral blood mononuclear cells (PBMCs) from steroid-sensitive (SS), steroid-dependent (SD) and steroid-resistant (SR) asthmatics patients, and to evaluate the role of GR and HSP90 in the pathogenesis of SR. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expressions of GR and HSP90 mRNA in PBMC stimulated with IL-2 and/or IL-4 from 10 normal volunteers, 10 SS, 5 SD and 6 SR patients. RESULTS: The expressions of GR and HSP90 mRNA were the highest in PBMC from SR patients (0.730 +/- 0.171 and 1.122 +/- 0.165, respectively) compared with the normals (P < 0.05). The second was from SS patients (0.359 +/- 0.350 and 0.885 +/- 0.250, respectively). The lowest was from the SD patients (0.017 +/- 0.008 and 0.078 +/- 0.039, respectively). The ratio of HSP90/GR in SR was significantly lower than that in the others, and it suggested that the expression of HSP90 mRNA was not sufficient in this group of patients. When PBMC from SS, SD and SR was incubated with IL-2 or IL-4 alone, no changes in GR and HSP90 mRNA expression were observed. While incubated with combination of IL-2 and IL-4, a significantly higher expression of GR mRNA was observed in all asthmatics, and a significantly higher expression of HSP90 mRNA was observed only in SS and SD patients. CONCLUSION: The lowering of HSP90/GR ratio may be one of the causes of SR. IL-2 and IL-4 may play roles in the imbalance of HSP90/GR.

Adult↗

[Changes of plasma p-selectin and nitric oxide in patients with pregnancy induced hypertension].

OBJECTIVE: To study the roles of P-selectin and nitric oxide (NO) on the etiology of pregnancy induced hypertension (PIH). METHODS: The levels of plasma P-selectin and nitrite and nitrate (NO2-/NO3-) were determined in 36 patients with PIH. The data were compared with those of normal pregnant group (n = 18) and healthy non-pregnant group (n = 19). The levels of plasma P-selectin were measured by means of enzyme-linked immunosorbent assay (ELISA) and levels of plasma NO2-/NO3- were measured by Griess reaction after the nitrate was reduced by a Cadmium-reduction method. RESULTS: The result showed: (1) The level of P-selectin in the normal pregnant group (48.92 +/- 15.16) micrograms/L was higher than that in non-pregnant group [(30.16 +/- 8.42) micrograms/L, P < 0.001]. There was no significantly statistical difference in the levels of P-selectin between the normal pregnant group and the mild PIH group (P > 0.05). The levels of P-selectin in the moderate and severe PIH group (70.11 +/- 17.65) micrograms/L were higher than those in the mild PIH group [(47.33 +/- 17.95) micrograms/L, P < 0.01] and the normal pregnant group (P < 0.001). (2) The concentration of NO2-/NO3- in normal pregnant group was higher than that in non-pregnant group (P < 0.01). The concentration of NO2-/NO3- in PIH group were lower than was in normal pregnant group (P < 0.001). The NO2-/NO3- in mild group was lower than that in normal pregnant group (P < 0.001). The Plasma concentration of NO2-/NO3- in moderate and severe PIH group was lower than that of mild group (P < 0.05). (3) There was a negative correlation between the plasma concentration of P-selectin and NO2-/NO3- in the PIH group. CONCLUSION: The changes of plasma levels of P-selectin and NO are related to the occurrence and development of PIH.

Adult↗

Detection of human herpesvirus 8 DNA in acute leukemia patients.

OBJECTIVE: To determine the prevalence of human herpesvirus 8 (HHV-8) DNA in acute leukemia (AL) patients. METHODS: The presence of HHV-8 DNA sequences in peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) from 50 AL patients was examined using polymerase chain reaction (PCR). Nine human hematopoietic cell lines and PBMC from 30 normal donors were also included. RESULTS: HHV-8 DNA sequences were detected in one case of acute myelogenous leukemia (AML). The specimens from the bone marrow aspirate, peripheral blood and serum of this patient were all positive. None of the normal donors and human hematopoietic cell lines showed evidence of HHV-8 DNA. CONCLUSION: The results suggest that the prevalence of HHV-8 is low in AL in China.

Acute Disease↗

Analysis of the T cell receptor V delta region gene repertoire in bronchoalveolar lavage fluid (BALF) and peripheral blood of asthmatics.

OBJECTIVE: To explore the role of gamma delta T cells in the airway of asthmatics and to identify the forces which induce and maintain the inflammatory process. METHODS: Peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were obtained from 7 asthmatic subjects and 7 nonsmoker control subjects. The percentage of gamma delta T cells in the PB and BALF was measured by immunofluorescent staining and flow cytometry. The frequency of usage and the clonality of V delta subfamilies (V delta 1-V delta 3) were assessed by RT-PCR and gene scanning. RESULTS: A higher proportion of gamma delta T cell was detected in the BALF of asthmatic subjects (7.8% +/- 4.7%) than that from control subjects (3.3% +/- 3.0%, P = 0.04). No selective usage for a particular V delta subfamily was found, but the relative expression level of V delta 1 was significantly higher in the asthmatic airway (44% +/- 13%) than in the control (19% +/- 5%, P = 0.0002). In asthmatic subjects, the monoclonal or oligoclonal expansion of gamma delta T lymphocytes was predominant in the BALF, especially V delta 1+ T lymphocytes. CONCLUSIONS: Antigenic specific gamma delta T cells might play an important role in the inducement and maintenance of airway inflammation. Persistent antigenic stimulation may be the key factor that maintains chronic airway inflammation in asthma.

Adult↗

Role of beta-adrenoceptor at different stages of bronchial asthma.

OBJECTIVE: To investigate the changes of beta-adrenergic receptor (beta AR) in peripheral lymphocytes and beta 2AR mRNA levels at different stages of bronchial asthma. METHODS: beta 2AR density and beta 2AR mRNA level in peripheral lymphocytes, cAMP and cGMP levels in blood plasma were estimated by radioligand binding assay, radioimmunoassay and RT-PCR. RESULTS: (1) Maximum bound volume (Bmax) and equilibrium dissociation constant (Kd) of beta 2AR of lymphocyte in asthma patients at remission stage were markedly higher than that in normal subjects, while cAMP levels in blood plasma showed no difference. Bmax of beta 2AR and cAMP levels in asthma patients at acute exacerbation stage were significantly lower than that in normal subjects, and Kds between these two groups were not much different. (2) Expression of beta 2ARmRNA in peripheral lymphocytes of asthmatics at remission stage was not significantly different compared with that in normals. CONCLUSIONS: Amount and function of beta AR and beta 2ARmRNA levels are related to asthmatic conditions. Changes of beta AR and beta 2ARmRNA in asthma might rather be a pathological change accompanied by the course of the disease than a primary defect.

Adult↗

[Analysis of the T cell receptor Vdelta region gene repertoire in asthmatic subjects].

OBJECTIVE: To explore the role of gammadelta T cells in the asthmatic airway inflammation and identify the forces which induce and maintain the inflammatory process. METHODS: Peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) were obtained from seven asthmatic subjects and seven nonsmoking control subjects. The percentage of gammadelta T cells in PB and BALF were measured by immunofluorescent staining and flow cytometry, the frequency of usage and the clonality of Vdelta subfamilies (Vdelta(1) approximately Vdelta(3)) were assessed by RT-PCR and gene scanning. RESULTS: Higher proportion of gammadelta T cell was detected in the BALF of asthmatic subjects [(7.8 +/- 4.7)%] than that from control subjects [(3.3 +/- 3.0)%] (P < 0.05) and the relative expression level of Vdelta(1) significantly higher in the asthmatic airway [(44 +/- 13)%] than in the control group [(19 +/- 5)%] (P = 0.002). In asthmatic subjects, the monoclonal or oligoclonal expansion of gammadelta T lymphocytes was predominant in BALF, especially Vdelta(1) T lymphocytes. CONCLUSIONS: Antigenic specific gammadelta T cells might play important roles in the inducement and maintenance of airway inflammation.

Adult↗