Biomedical subjects

J Zhao

Publications and source records attributed to J Zhao.

At least 73 records · Page 4Linked to original sources

PubMed2003

Global metabolic response of Escherichia coli to gnd or zwf gene-knockout, based on 13C-labeling experiments and the measurement of enzyme activities.

An integrated study on cell growth, enzyme activities and carbon flux redistribution was made to investigate how the central metabolism of Escherichia coli changes with the knockout of genes in the oxidative pentose phosphate pathway (PPP). Mutants deficient in glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were constructed by disrupting the zwf and gnd genes and were grown in minimal media with two different carbon sources, such as glucose or pyruvate. It was shown that the knockout of either gnd or zwf gene did not affect the cell growth rate significantly, but the cellular metabolism was changed. While the specific substrate uptake rate and the specific carbon dioxide evolution rate for either mutant grown on glucose were higher than those obtained for the parent strain, these two rates were markedly decreased in mutants grown on pyruvate. The measurement of enzyme activities implied a significant change in metabolism, when alternative pathways such as the Entner-Doudoroff pathway (EDP) and the malic enzyme pathway were activated in the gnd mutant grown on glucose. As compared with the parent strain, the activities of phosphoglucose isomerase were increased in mutants grown on glucose but decreased in mutants grown on pyruvate. The metabolic flux redistribution obtained based on 13C-labeling experiments further indicated that the direction of the flux through the non-oxidative PPP was reversed in response to the gene knockout. Moreover, the knockout of genes caused an increased flux through the tricarboxlic acid cycle in mutants grown on glucose but caused a decrease in the case of using pyruvate. There was also a negative correlation between the fluxes through malic enzyme and isocitrate dehydrogenase in the mutants; and a positive correlation was found between the fluxes through malic enzyme and phosphoenolpyruvate carboxylase.

Carbohydrate Metabolism↗

PubMed2003

Biomechanical and morphometric intestinal remodelling during experimental diabetes in rats.

AIMS/HYPOTHESIS: Morphometric and passive biomechanical properties were studied in the duodenum, jejunum and ileum in 10 non-diabetic and 40 streptozotocin-induced diabetic rats. METHODS: The diabetic rats were divided into groups living 4 days, 1, 2, and 4 weeks after diabetes was induced ( n=10 for each groups). The mechanical test was done as a ramp distension experiment. The intestinal diameter and length were obtained from digitised images of the intestinal segments at pre-selected pressures and at no-load and zero-stress states. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter and pressure data and from the zero-stress state geometry. RESULTS: The blood glucose concentration increased four- to fivefold in the diabetic rats. Streptozotocin-induced diabetes generated pronounced increase in the weight per centimetre length, wall thickness and wall cross-sectional area in all intestinal segments during diabetes ( p<0.05). Histological analysis showed that the thickness of the intestinal layers was increased in all segments during diabetes ( p<0.05). In the duodenum the opening angle did not change in the first 2 weeks and decreased after 4 weeks ( p<0.05). In the jejunum and ileum the opening angle increased after 1 week in the diabetic group. The residual strain showed the same pattern as the opening angle. Furthermore, it was found that the circumferential and longitudinal stiffness of the intestinal wall increased with the duration of diabetes ( p<0.05 and p<0.01). CONCLUSION/INTERPRETATION: Morphological and biomechanical remodelling of the small intestine occurred during the development of diabetes.

Animals↗

PubMed2003

Esomeprazole administered through a nasogastric tube provides bioavailability similar to oral dosing.

AIM: To determine if nasogastric tube administration of the enteric-coated pellets from an opened esomeprazole capsule provides bioavailability similar to oral dosing with the intact capsule. METHODS: A randomized, single-centre, open-label, two-period crossover pharmacokinetic study consisting of two 5-day dosing periods separated by a 7- to 14-day washout period was conducted. Healthy subjects between the ages of 18 and 50 years received esomeprazole 40 mg once daily either orally as an intact capsule, or as a suspension of the enteric-coated pellets from an opened capsule in water through a nasogastric tube. RESULTS: In 47 evaluable subjects, the 90% confidence intervals were 0.87-1.08 and 0.93-1.25 for the geometric mean of the ratio of nasogastric tube administration relative to administration of the intact capsule for the area under the plasma concentration-time curve and for maximum plasma concentration, respectively, on day 1, demonstrating bioequivalence. Oral and nasogastric administration also demonstrated similar bioavailabilities on day 5. Esomeprazole was well tolerated regardless of the mode of administration. CONCLUSIONS: Nasogastric tube administration of the enteric-coated pellets from an opened esomeprazole 40 mg capsule provides bioavailability similar to oral dosing. Administration of the contents of an opened esomeprazole 40 mg capsule in water through a nasogastric tube is a practical alternative for patients with feeding tubes who require effective gastric acid suppression, but cannot swallow an oral preparation.

Administration, Intranasal↗

PubMed2003

The effect of epidermal growth factor on the incremental Young's moduli in the rat small intestine.

Biomechanical remodelling of the rat small intestine after treatment with epidermal growth factor (EGF) subcutaneously for 2 days (n=6), 4 days (n=6), 7 days (n=6), and 14 days (n=4) was studied. The incremental circumferential, longitudinal and cross moduli close to the in vivo state were computed from bi-axial test data (combined inflation and axial stretching) by a least square method. The moduli in the circumferential direction and the longitudinal direction differed in all groups, i.e. the mechanical properties were anisotropic in both normal and EGF-treated rats. Time-dependent variation existed for the Young's moduli in all directions during EGF treatment (P<0.05). The circumferential modulus decreased during the first 7 days of EGF treatment and it almost remodelled back to that of the control group after 14 days treatment. The incremental modulus in the circumferential direction ranged between 17.4 and 24.2 kPa. The modulus in the longitudinal direction ranged between 22.9 and 32.4 kPa. The longitudinal modulus after 4 days EGF treatment was significantly larger than that of control group (P<0.02). The cross modulus decreased during the first 4 days of EGF treatment thereafter it increased to a maximum at 7 days. The values for the cross moduli were between 4.7 and 6.6 kPa. In conclusion, the mechanical properties in the intestinal wall are anisotropic and remodel during treatment with EGF.

Adaptation, Physiological↗

PubMed2003

Respiratory burst activity of polymorphonuclear cells is dependent on the cell preparation technique.

BACKGROUND: Controversial results have been reported regarding the effect of anaesthetics on superoxide anion production during the respiratory burst (RB) of polymorphonuclear cells (PMN). The differences could be caused by the cell preparation methods and the aim of this study was to compare two techniques. METHODS: RB activity was measured in cell suspensions isolated with the single-step Ficoll procedure and in unfractionated whole blood. Two concentrations of propofol (therapeutic and 10-fold of this, 6 microg ml-1 or 60 microg ml-1) were investigated after cell preparation with both methods. RB was stimulated with Escherichia coli (E. coli), phorbol 12-myristate 13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) and measured by means of fluorescence intensity in a flow cytometer. RESULTS: The percentage of PMNs in whole blood which generate superoxide anions in response to fMLP was significantly lower (2.5 +/- 0.7%; mean +/- SEM) than that in Ficoll isolated cell suspensions (15.1 +/- 1.7%). Incubation with propofol led to a concentration-related decrease of RB activity in Ficoll separated PMNs after both PMA and fMLP stimulation. No significant effect of propofol was observed on the RB in PMA stimulated whole blood samples. CONCLUSION: The results suggest that the influence of cell preparation methods should be considered when the in vitro effects of anaesthetics on PMN functions are studied with flow cytometric methods.

Anesthetics, Intravenous↗

PubMed2003

[Differential gene expression signatures in well differentiated thyroid carcinomas].

Despite their common origin from follicular epithelial cells, papillary and follicular thyroid carcinomas differ in their histology and clinical course. In this study the transcriptional profiles of these tumors in comparison with normal thyroid tissue were established. The aim was the development of a molecular tool providing additional information to current histopathological diagnosis and allowing further insight into tumorigenesis. Genome wide expression profiling was performed using Human Unigene Set--RZPD 2 high density cDNA macroarrays comprising 76,000 genes as probes and radioactively labeled cDNA targets retrotranscribed from the isolated RNA of three papillary and three follicular thyroid carcinomas as well as three normal thyroid tissues. 8600 genes differing in their expression between the three groups were selected and printed onto subarrays. Radioactively labeled cDNA targets obtained from 16 papillary carcinomas, 13 follicular carcinomas and 17 normal thyroid tissues were hybridized to these subarrays. 200 genes exhibited a statistically significant expression difference between the two tumor types (p <0.01). In a hierarchical cluster analysis of 124 of these genes (46 known genes and 78 ESTs) the algorythm divided the tumor samples into two groups corresponding to the papillary and follicular thyroid carcinomas. The clearcut diagnostic potential of this method has to be corroborated in a prospective study. Several of the differentiallly expressed genes are known to play a role in tumor development and metastasis. Some of the genes up- or down-regulated in both tumor types are members of known oncogenic pathways in thyroid carcinomas. The complete understanding of complex genome wide expression profiles however awaits a longstanding advancement of hypothesis driven research.

DNA, Neoplasm↗

PubMed2002

The generation of oxygen radicals after drinking of oxygenated water.

UNLABELLED: It has been speculated whether ingestion of oxygenated water can lead to an enhanced generation of oxygen radicals. The purpose of three prospective randomized blinded clinical studies was therefore to measure if, when and at which oxygen content in the water,drinking of oxygenated water induces the generation of radicals. Moreover in the fourth prospective,randomized, blinded study possible longterm effects of drinking oxygenated water were examined. METHODS: Altogether 66 volunteers were drinking 300 ml oxygenated or tap water within 15 minutes. Before drinking, altogether 15 ml of blood from the antecubital vein was collected for determination of ascorbyl radicals with ESR, routine laboratory data (hemoglobin, erythrocytes, hematocrit, leukocytes, thrombocytes, uric acid) and the vitamins A,C,E by HPLC. After drinking the ascorbyl radical measurements were repeated from blood of the antecubital vein. In the longterm study ( fourth study) the volunteers had to undergo the same procedure, as described above, at day 1 and day 21. In the meantime they were drinking per day three times 300 ml either oxygenated water or tap water. RESULTS: All subjects exhibited normal vitamin levels in all three studies. Concommitantly in the fourth study there was no statistically relevant alteration of vitamin concentrations during the observation period of three weeks in the verum and placebo-group. 30 minutes after drinking oxygenated water the concentration of ascorbyl radicals increased significantly by median 42 % from median 48 to 65 nmol/l. This increase of ascorbyl radicals after 30 minutes was reproducible in all studies. The levels of ascorbyl radicals remained elevated for 60 minutes after drinking and returned to normal after 120 minutes. This increase was independent of the oxygen concentration in the water, beginning at 30 mg oxygen/l. Water containing 15 mg oxygen/l did not lead to an enhanced radical formation. Longterm consumption of oxygenated water attenuated the ascorbyl radical increase normally observed, thus the initial increase of ascorbyl radicals at day 1 could not be observed after day 21, if the subjects were drinking oxygenated water regularly during the observation period. CONCLUSION: Drinking of oxygenated water possibly leads to a time-limited, yet very moderate, systemic generation of radicals. Regular consumption of oxygenated water over a longer period of time seems to attenuate this effect. The mechanisms leading to this effect and adaptation are unknown.

Adult↗

PubMed2002

Hypericum perforatum--chemical profiling and quantitative results of St. John's Wort products by an improved high-performance liquid chromatography method.

The analysis of flavonoids, naphthodianthrones, and the phloroglucinol derivative hyperforin in H. perforatum is described in this article. In a 35-min HPLC run nine major compounds could be identified and baseline separated in the methanolic plant extracts. For an optimum separation the mobile phase consisted of 10 mM ammonium acetate buffer (pH 5.0) and an acetonitrile/methanol mixture; a Synergi MAX-RP 80 A column (C-12 material) was used as stationary phase. Detection was performed at 270 nm, and the identity of the compounds was confirmed in an LC-MS experiment. Commercial St. John's Wort products were analyzed and qualitative and quantitative results are discussed.

Calibration↗

PubMed2002

Remodelling of zero-stress state of small intestine in streptozotocin-induced diabetic rats. Effect of gliclazide.

BACKGROUND: Biomechanical properties in terms of residual strains in diabetic small intestine have not been studied. Furthermore, no data have been reported on affect of gliclazide on gastrointestinal complications of diabetes. AIMS: To determine remodelling of zero-stress state of small intestine in streptozotocin-induced diabetic rats and effect of gliclazide treatment. MATERIALS: Morphological properties and residual strains were studied in duodenum, jejunum and ileum obtained from diabetic rats, gliclazide-treated diabetic rats and normal rats (n = 8 each group). METHODS: Diabetes was induced by single intraperitoneal injection of 65 mg/kg streptozotocin. Gliclazide (10 mg kg(-1) day(-1) was injected directly into stomach lumen by intragastric gavage twice daily. Experimental period was 35 days. To approach no-load state; intestinal segments were surgically excised and cut transversely into short ring-shaped segments. Each ring was cut radially to obtain geometry of zero-stress state. Circumferential length, the wall thickness and opening angle were measured from digital images of each specimen and residual strains were computed. RESULTS: Blood glucose level of diabetic group (approximately 20 mmol/l) was consistently higher than that in normal group (approximately 4 mmol/l) after induction of diabetes (p < 0.001). Gliclazide lowered average blood glucose level to between 10 and 15 mmol/l (p < 0.001). Plasma insulin levels of both diabetic groups (average between 10 and 15 pmol/l) were significantly lower than those in normal group (average approximately 18 pmol/l, p < 0.05). Wet weight per unit length and wall thickness of duodenum, jejunum and ileum were significantly higher in Diabetes group than those in Normal group (p < 0.05). Opening angle and absolute value of residual strain were significantly smaller in duodenum and larger in jejunum and ileum in Diabetes group than in Normal group (p < 0.001). Gliclazide treatment partly restored these changes (p < 0.05). CONCLUSIONS: Diabetes induced morphometric and biomechanical remodelling in intestine. Gliclazide partly restored these changes.

Animals↗

PubMed2002

Immunohistochemical localisation of growth hormone (GH), GH receptor (GHR), insulin-like growth factor I (IGF-I) and type I IGF-I receptor, and gene expression of GH and GHR in rat pre-antral follicles.

We previously demonstrated that the development of cultured rat pre-antral follicles is stimulated by growth hormone (GH) and insulin-like growth factor-I (IGF-I) and that the mRNA of IGF-I and type I IGF receptor (IGFR) is present in the oocyte and wall of these follicles. To gain a closer insight into the regulation of early folliculogenesis by GH and IGF-I, the present study investigated the gene expression of GH and GHR mRNA in isolated oocytes and follicular wall cells of pre-antral follicles, using reverse transcriptase polymerase chain reaction, and the localisation of immunoreactive IGF-I, IGFR, GH and GHR proteins in ovarian sections of 10-day-old rats. GH was detected in oocytes and follicular wall tissue of pre-antral follicles, whereas expression of the GH mRNA was absent. The GHR mRNA was present in follicular wall tissue and not in the oocyte, while positive immunostaining for GHR was observed in all cells of the pre-antral follicles. Immunoreactive IGF-I and IGFR was also visible in the pre-antral follicles, especially in the oocytes. In conclusion, the data show that the previously demonstrated local gene expression of IGF-I and IGFR in oocytes and their enveloping follicular cells also leads to translation, which points to the involvement of intrafollicular IGF-I in early follicular development. The presence of the GHR mRNA and the GHR and GH proteins in pre-antral follicles in the absence of ovarian GH mRNA suggest a direct effect of systemic GH on early follicular development.

Animals↗

PubMed2002

Morphometric and biomechanical remodelling in the intestine after small bowel resection in the rat.

The short-bowel syndrome is a clinical condition caused by intestinal resection. As intestinal adaptation occurs after resection, it can be used as a model for studying morphometric and biomechanical remodelling in the small intestine and to get a better understanding of the pathophysiology of the short-bowel syndrome. The resected rats had a 67% resection of jejunum and ileum. Control animals underwent no operation (nonoperated controls) or an ileal transection with subsequent end-to-end anastomosis (sham-resected controls). The animals were followed for up to 4 weeks after the operation. Changes in biomechanical properties were studied in terms of residual strain (the internal strain remaining when all external loads are removed), opening angle and stress--strain relations referenced to the zero-stress state (the cut-open state where external and internal stresses are released). The resected animals gained less weight than the controls. The intestinal length and diameter increased more in the resected groups than the control groups (P < 0.05), resulting in a larger absorptive surface. Resection induced profound gross morphometric changes and histological alterations characterized by proliferative increases in the tissue layers. The opening angle, along with residual strain at the mucosal and serosal surface, increased in the remnant small intestine (P < 0.05). All changes increased as function of postoperative time and were most prominent in the remnant ileum. However, the stress-strain relationship remained unchanged. In conclusion, this study demonstrated that resection of the majority of the small bowel results in significant remodelling in structural and residual strain properties in the remnant small intestine. The remodelling seems to be guided by the need for a greater absorptive surface area rather than for a change in the stress-strain properties.

Adaptation, Physiological↗

PubMed2002

Influence of readout parameters on TL response, re-usability and residual signal in LiF:Mg,Cu,P.

It has recently been recommended that heating rates do not exceed 10 K.s(-1) and that the maximum temperature of readout should not exceed 265 degrees C for LiF:Mg,Cu,P. In some cases, a decrease of sensitivity in this material in the first of several re-use cycles had been reported. Influence of heating rates up to 30 K.s(-1), duration time up to 40s and maximum readout temperatures up to 270 degrees C on TL response, re-usability and residual signal was investigated. It was found that the maximum readout temperatures above 240 degrees C may lead to the thermoluminscent response decrease in the first several re-use cycles. The readout parameters can be optimised to minimise the residual signal (less than 0.4%) and to retain a constant sensitivity at the same time at high heating rates up to 30 K.s(-1) in a short time (less than 1 min per TL chip) without the necessity of heating above 240 degrees C. A concept of 'efficient residual signal' was put forward to quantify more accurately the real residual signal which affects the precision of the next measurement.

Copper↗

PubMed2002

Testosterone and estradiol modulate TNF-alpha-induced expression of adhesion molecules in endothelial cells.

Cytokine-activated endothelial expression of adhesion molecules plays an important role in immune responses. In the present study, we investigated the influences of testosterone and 17 beta-estradiol on tumor necrosis factor-alpha (TNF-alpha)-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVEC). HUVEC were incubated with TNF-alpha, testosterone or 17 beta-estradiol separately, or in a combination of TNF-alpha plus testosterone or 17 beta-estradiol. The expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was evaluated at 3, 6, 12 and 24 h following exposure by flow cytometric analysis. The results showed that although testosterone or 17 beta-estradiol did not affect the expression of these adhesion molecules in unstimulated HUVEC, both of them transiently increased the expression of E-selectin and VCAM-1 in TNF-alpha stimulated HUVEC. Neither testosterone nor 17 beta-estradiol affected the expression of ICAM-1 induced by TNF-alpha. It is concluded that both testosterone and 17 beta-estradiol increase TNF-alpha-induced expression of E-selectin and VCAM-1 in endothelial cells and these facts might indicate a mechanism by which gonadal hormones can indirectly enhance immune responses.

Cells, Cultured↗

PubMed2002

The effects of cigarette smoke extract on the endothelial production of soluble intercellular adhesion molecule-1 are mediated through macrophages, possibly by inducing TNF-alpha release.

Cigarette smoke (CS) is a major risk factor for many human diseases, although the underlying mechanisms are not clearly understood. This study was undertaken to investigate the effect of a water-soluble CS extract (CSE) on soluble intercellular adhesion molecule-1 (sICAM-1) production by human umbilical vein endothelial cells (HUVEC) mediated through ANA-1 macrophages. First, macrophages were incubated with or without CSE, and the supernatants collected at different time points were used to measure the levels of tumor necrosis factor-alpha (TNF-alpha) and sICAM-1 by enzyme-linked immunosorbent assay (ELISA); and second, HUVEC were cultured with CSE, a vehicle, or ANA-1 supernatants (collected at different time points) and the sICAM-1 levels in the supernatants were measured by ELISA at 24 h. The results showed that: i) CSE showed no effect on the production of sICAM-1 by HUVEC; ii) sICAM-1, in unstimulated or CSE-stimulated ANA-1 supernatants collected at different time points, was under the detectable level; iii) CSE-stimulated ANA-1 supernatants collected at 3 or 6 h showed no effect on sICAM-1 production in HUVEC, while those collected at 12 and 24 h significantly increased sICAM-1 production (p < 0.02 and p < 0.005, respectively); iv) no significant difference in TNF-alpha levels was detected between unstimulated and CSE-stimulated macrophage supernatants collected at 3 and 6 h, however, higher levels of TNF-alpha were found in CSE-stimulated supernatants collected at 12 and 24 h (p < 0.05 and p < 0.002, respectively); and v) a significant correlation (r = 0.9693, p < 0.001) was found between the levels of TNF-alpha in CSE-stimulated ANA-1 supernatants and those of related sICAM-1 production in HUVEC. These findings indicate that CSE indirectly increases the production of sICAM-1 in HUVEC by activating macrophages, which possibly induces the release of TNF-alpha from them, which in turn enhances the production of sICAM-1 from HUVEC.

Cells, Cultured↗

PubMed2001

[New type pathogenic mycoplasmas isolated from female patients with genital infection in Nanjing, China].

OBJECTIVE: To study if infection of new type pathogenic mycoplasmas, Mycoplasma penetrans (Mpe), Mycoplasma fermentans (Mf), and Mycoplasma pirum (Mpi), exists in the genital tract of gynecologic patients with genital infection in China so as to provide information for clinical diagnosis and therapy. METHODS: Cervical secretions from 172 patients with infectious diaseses of gentital tract and 172 healthy controls were collected and inoculated in improved SP-4 culture medium. Biochemical reaction, coagglutination test, metabolism-inhibition test, polymerase chain reaction (PCR) assay, and DNA sequencing were employed to identify the isolated microorganisms. RESULTS: One strain of Mycoplasma penetrans (0.58%) and two strains of Mycoplasma fermentans (1.16%) were isolated from the cervical secretions of patients, but none was found in healthy controls. CONCLUSION: Mpe infection and Mf infection exist in female patients with genital infection in Nanjing.

Adult↗

PubMed2001

Telomerase-specific suicide gene therapy vectors expressing bacterial nitroreductase sensitize human cancer cells to the pro-drug CB1954.

Telomerase activation is considered to be a critical step in cancer progression due to its role in cellular immortalization. The prevalence of telomerase expression in human cancers makes it an attractive candidate for new mechanism-based targets for cancer therapy. The selective killing of cancer cells can be achieved by gene-directed enzyme pro-drug therapy (GDEPT). In this study we have tested the feasibility of using the transcriptional regulatory sequences from the hTERT and hTR genes to regulate expression of the bacterial nitroreductase enzyme in combination with the pro-drug CB1954 in a suicide gene therapy strategy. hTERT and hTR promoter activity was compared in a panel of 10 cell lines and showed a wide distribution in activity; low activity was observed in normal cells and telomerase-negative immortal ALT cell lines, with up to 300-fold higher activity observed in telomerase positive cancer lines. Placing the nitroreductase gene under the control of the telomerase gene promoters sensitized cancer cells in tissue culture to the pro-drug CB1954 and promoter activity was predictive of sensitization to the pro-drug (2-20-fold sensitization), with cell death restricted to lines exhibiting high levels of promoter activity. The in vivo relevance of these data was tested using two xenograft models (C33a and GLC4 cells). Significant tumour reduction was seen with both telomerase promoters and the promoter-specific patterns of sensitization observed in tissue culture were retained in xenograft models. Thus, telomerase-specific suicide gene therapy vectors expressing bacterial nitroreductase sensitize human cancer cells to the pro-drug CB1954.

Animals↗

PubMed2001

Do lung remodeling, repair, and regeneration recapitulate respiratory ontogeny?

Herein we posit that modeling of the lungs during morphogenesis, repair, and regeneration is tightly coordinated by conserved stimulatory and inhibitory signaling mechanisms, including specific transcriptional factors, cytokines, peptide growth factors, proteases, and matrix elements. This evolutionary-developmental (evo-devo) functional conservation has been extended to morphogenesis of the respiratory tracheae in Drosophila. Fifty or more genes direct fruit fly tracheal organogenesis. Among them, hedgehog, patched, smoothened, cubitus interruptus, branchless, breathless, sprouty, decapentaplegic, and mad are functionally conserved between flies, mice, and humans. For example, fibroblast growth factor (FGF) signaling is essential, not only for fly trachea and mouse bronchial branching morphogenesis, but also for postnatal modeling and repair of alveoli. Likewise, sprouty family genes act as inducible negative regulators of FGF signaling, which in part may determine interbranch length during bronchial development. Alveolar epithelial survival, migration, and proliferation during remodeling after hyperoxic injury also require FGF signaling. In addition, FGF signaling appears to regulate a small (< 5%) population of putative alveolar stem/ progenitor cells that express telomerase and are relatively resistant to hyperoxic apoptosis. We speculate that genes in evo-devo functionally conserved signaling pathways such as FGF-FGF receptor-Sprouty may provide novel therapeutic targets to augment lung repair and induce lung regeneration.

Adult↗

PubMed2001

The microtubule associated protein Tau gene and Alzheimer's disease--an association study and meta-analysis.

Several studies have suggested an association between polymorphisms and an extended haplotype of the microtubule associated protein tau gene and Alzheimer's disease (AD) in synergy with apolipoprotein E (APOE) epsilon 4 status. However these findings have not been consistently replicated. We investigated the role of the tau haplotype in AD by conducting an association study as well as a meta-analysis of all the studies conducted to date. We examined six polymorphisms known to be in the extended tau haplotypes, one in exon 7 and five in and around exon 9 in 200 late onset AD and 189 control samples. All the polymorphisms examined fell into the recognised tau haplotypes. There was no statistical significant association with any of the polymorphisms and late onset AD. Stratification of data by APOE epsilon 4 status also produced no strongly significant association. The meta-analysis showed no significant differences between AD cases and controls, however stratification of data by APOE epsilon 4 status showed a small significant decrease in the H1 haplotype in AD before correction for multiple testing.

Aged↗