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Biomedical subjects

A Li

Publications and source records attributed to A Li.

At least 19 recordsLinked to original sources
PubMed2006

Culture of zygotes increases TRP53 [corrected] expression in B6 mouse embryos, which reduces embryo viability.

The expression of TRP53 in blastocysts that had been cultured from the zygote stage in vitro for 90 h was compared with that in blastocysts collected from the uterus in C57BL6 (B6) and in F1 hybrid (B6CBF1) strain mice. In both strains, there was little TRP53 detected in blastocysts collected from the uterus. There was some increased expression in cultured embryos from B6CBF1 mice and marked increased expression in cultured B6 blastocysts. In cultured B6 embryos, there was obvious accumulation of TRP53 within the nuclear region of embryonic cells. Cultured B6 zygotes had significantly poorer rates of blastocyst formation and of capacity to undergo implantation or form viable fetuses than cultured zygotes from B6CBF1 mice or B6 blastocysts collected from the uterus. Trp53-/- zygotes (B6 background) were significantly more likely to form blastocysts than sibling wild-type embryos, with Trp53+/- embryos having an intermediate level of viability (P<0.01). On transfer of blastocysts to recipient females, Trp53-/- blastocysts were more likely to form viable fetuses than wild-type or heterozygous sibling blastocysts when the embryos resulted from culture of zygotes (P<0.001). This shift in viability did not occur when embryos were only subjected to 24 h of culture from the compacted embryo stage. Culture in vitro in the B6 strain caused a marked increase in the expression and nuclear accumulation of TRP53. This expression was a significant cause of the loss of viability that occurs on culture of zygotes from this strain in vitro.

Animals↗
PubMed2006

High-peak-power AlGaInAs quantum-well 1.3-mum laser pumped by a diode-pumped actively Q-switched solid-state laser.

We report a room-temperature high-peak-power AlGaInAs 1.36 microm TEM00 laser pumped by a diode-pumped actively Q-switched Nd:YAG 1.06 microm laser. With an average pump power of 1.0 W, an average output power of 140 mW was obtained at a pulse repetition rate of 10 kHz. With a peak pump power of 8.3 kW, the highest peak output power was 1.5 kW at a pulse repetition rate of 5 kHz.

Journal Article↗
PubMed2006

Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets.

Acute inhibition of serotonergic (5-HT) neurons in the medullary raphé (MR) using a 5-HT(1A) receptor agonist had an age-dependent impact on the "CO(2) response" of piglets (33). Our present study explored the effect of chronic 5-HT neuron lesions in the MR and extra-raphé on the ventilatory response to hypercapnia and hypoxia in piglets, with possible implications on the role of 5-HT in the sudden infant death syndrome. We established four experimental groups. Group 1 (n = 11) did not undergo any treatment. Groups 2, 3, and 4 were injected with either vehicle or the neurotoxin 5,7-dihydroxytryptamine in the cisterna magna during the first week of life (group 2, n = 9; group 4, n = 11) or second week of life (group 3, n = 10). Ventilation was recorded in response to 5% CO(2) (all groups) and 12% O(2) (group 2) during wakefulness and sleep up to postnatal day 25. Surprisingly, the piglets did not reveal changes in their CO(2) sensitivity during early postnatal development. Overall, considerable lesions of 5-HT neurons (up to 65% decrease) in the MR and extra-raphé had no impact on the CO(2) response, regardless of injection time. Postlesion raphé plasticity could explain why we observed no effect. 5,7-Dihydroxytryptamine-treated males, however, did present a lower CO(2) response during sleep. Hypoxia significantly altered the frequency during sleep in lesioned piglets. Further studies are necessary to elucidate the role of plasticity, sex, and 5-HT abnormalities in sudden infant death syndrome.

5,7-Dihydroxytryptamine↗
PubMed2006

Vascular endothelial growth factor mediates atorvastatin-induced mammalian achaete-scute homologue-1 gene expression and neuronal differentiation after stroke in retired breeder rats.

Neurogenesis declines with advancing age. The mammalian achaete-scute homologue-1 encodes a basic helix-loop-helix transcription factor, which controls neuronal differentiation. In this study, we first tested whether atorvastatin treatment enhances neurological functional outcome and neuronal differentiation after stroke in retired breeder 12 month rats. Rats were subjected to middle cerebral artery occlusion and treated with or without atorvastatin (3 mg/kg) for 7 days. Atorvastatin significantly increased expression of mammalian achaete-scute homologue-1, beta-tubulin III, and vascular endothelial growth factor in the ischemic brain, and concomitantly improved functional outcome compared with middle cerebral artery occlusion control rats. Increased neurogenesis significantly correlated with functional recovery after stroke. To further investigate the mechanisms of atorvastatin-induced neuronal differentiation, experiments were performed on neurospheres derived from retired breeder rat subventricular zone cells. Atorvastatin increased neuronal differentiation and upregulated vascular endothelial growth factor and mammalian achaete-scute homologue-1 gene expression in cultured neurospheres. Vascular endothelial growth factor-treated neurospheres significantly increased mammalian achaete-scute homologue-1 and beta-tubulin III expression. Inhibition of vascular endothelial growth factor decreased atorvastatin-induced mammalian achaete-scute homologue-1 and beta-tubulin III expression. These data indicate that atorvastatin increases neuronal differentiation in retired breeder rats. In addition, atorvastatin upregulation of vascular endothelial growth factor expression, influences mammalian achaete-scute homologue-1 transcription factor, which in turn, facilitates an increase in subventricular zone neuronal differentiation. These atorvastatin-mediated molecular events may contribute to the improved functional outcome in retired breeder rats subjected to stroke.

Analysis of Variance↗
PubMed2006

Co-transplantation of bone marrow stromal cells transduced with IL-7 gene enhances immune reconstitution after allogeneic bone marrow transplantation in mice.

Allogeneic bone marrow transplantation (allo-BMT) is followed by a period of profound immune deficiency, which results in significant susceptibility to infections and limits the extensive application of this approach in clinic. Here, we transduced human interleukin-7 (IL-7) gene into donor-derived bone marrow stromal cells (MSCs) using adenovirus vector, and transplanted this gene-engineered MSCs (MSC-IL-7) into lethally irradiated C57BL/6 mice to investigate their effects on immune reconstitution following allo-BMT. Recipient mice receiving MSC-IL-7 cells plus T-cell-depleted bone marrow cells of BALB/c mice showed a significant increase in thymopoiesis and homeostatic expansion of peripheral T lymphocytes. Furthermore, injection of MSC-IL-7 cells following allo-BMT protected the host from the lethality caused by acute graft-versus-host disease (GVHD) and prevented the occurrence of GVHD induced by transplanted T cells. Thus, the use of MSC-IL-7 cells may be therapeutically useful for enhancing immune reconstitution without aggravating GVHD in allo-BMT mice.

Adenoviridae↗
PubMed2006

N-cadherin mediates nitric oxide-induced neurogenesis in young and retired breeder neurospheres.

Neurogenesis may contribute to functional recovery after neural injury. Nitric oxide donors such as DETA-NONOate promote functional recovery after stroke. However, the mechanisms underlying functional improvement have not been ascertained. We therefore investigated the effects of DETA-NONOate on neural progenitor/stem cell neurospheres derived from the subventricular zone from young and retired breeder rat brain. Subventricular zone cells were dissociated from normal young adult male Wistar rats (2-3 months old) and retired breeder rats (14 months old), treated with or without DETA-NONOate. Subventricular zone neurosphere formation, proliferation, telomerase activity, and Neurogenin 1 mRNA expression were significantly decreased and glial fibrillary acidic protein expression was significantly increased in subventricular zone neurospheres from retired breeder rats compared with young rats. Treatment of neurospheres with DETA-NONOate significantly decreased neurosphere formation and telomerase activity, and promoted neuronal differentiation and neurite outgrowth concomitantly with increased N-cadherin and beta-catenin mRNA expression in both young and old neurospheres. DETA-NONOate selectively increased Neurogenin 1 and decreased glial fibrillary acidic protein mRNA expression in retired breeder neurospheres. N-cadherin significantly increased Neurogenin 1 mRNA expression in young and old neurospheres. Anti-N-cadherin reversed DETA-NONOate-induced neurosphere adhesion, neuronal differentiation, neurite outgrowth, and beta-catenin mRNA expression. Our data indicate that age has a potent effect on the characteristics of subventricular zone neurospheres; neurospheres from young rats show significantly higher formation, proliferation and telomerase activity than older neurospheres. In contrast, older neurospheres exhibit significantly increased glial differentiation than young neurospheres. DETA-NONOate promotes neuronal differentiation and neurite outgrowth in both young and older neurospheres. The molecular mechanisms associated with the DETA-NONOate modulation of neurospheres from young and older animals as well age dependent effects of neurospheres appear to be controlled by N-cadherin and beta-catenin gene expression, which subsequently regulates the neuronal differentiating factor Neurogenin expression in both young and old neural progenitor cells.

Aging↗
PubMed2006

Electron beam damage studies of synthetic 6-line ferrihydrite and ferritin molecule cores within a human liver biopsy.

In order to achieve an accurate understanding of the crystal structure of 6-line ferrihydrite (6LFh) and ferritin molecule cores within a human liver biopsy using transmission electron microscopy (TEM), electron beam damage should be considered. For the case of 6LFh, the electron energy loss near-edge structure (ELNES) of core ionisation edges in the electron energy loss spectrum (EELS) combined with multiple linear least-square (MLLS) fitting of reference spectra together with analysis of selected area electron diffraction (SAED) patterns suggests that the iron in 6LFh is solely octahedrally coordinated Fe3+. With increasing electron dose, an increasing percentage of this octahedrally coordinated Fe3+ migrates to tetrahedral sites. When the dose exceeds 3 x 10(8) electrons/nm2, Fe2+ is found to be present in the material. This method also indicates that the iron in ferritin molecule cores within a human liver biopsy is the same as in 6LFh, entirely Fe3+ in octahedral coordination with oxygen. Again the percentage of octahedrally coordinated Fe3+ decreases as the accumulated electron dose increases and Fe2+ is produced in the liver biopsies when the electron dose exceeds 10(6)electrons/nm2.

Adult↗
PubMed2006

Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF.

Our previous study showed that DNA vaccination with a plasmid vector encoding a core peptide of mucin1 (PDTRP) provided modest protection against challenge with tumor cells that expressed mucin1 protein. We report here that a DNA vaccine comprising a modified PDTRP plasmid and GM-CSF coding sequence at the C-terminus induced better protection against tumor challenge. The increased protection was directly correlated with a stronger PDTRP-specific immune response induced by the GM-CSF fusion plasmid. The plasmid encoding GM-CSF and the target PDTRP antigen induced a greater PDTRP-specific Th proliferation, antibodies, and cytotoxicity. Interestingly, the modified plasmid vaccine predominantly enhanced the type 2 immune responses manifested by an increased IgG1 to IgG2a antibody ratio and a greater induction of GATA-3 and IL-4 mRNA than that of T-bet and IFN-gamma mRNA in spleen cells from vaccinated mice. In addition, protection against tumor challenge in vaccinated mice showed that there was no significant change in mice survival after in vivo CD8+CTL depletion, indicating that antitumor immunity augmented by plasmid encoding GM-CSF and target PDTRP gene vaccine was dominated by Th2 immune response.

Animals↗
PubMed2006

Acute adverse reactions to magnetic resonance contrast media--gadolinium chelates.

The objective of this study was to evaluate the clinical safety of intravenous gadolinium-based contrast media used in patients who underwent MRI at a single institution. Acute adverse reactions to intravenous gadolinium-based contrast media used for MRI at the Princess Margaret Hospital, Hong Kong, SAR, from January 1999 to November 2004 were recorded in an incidence log book. The medical records of patients' demographics were retrospectively reviewed and the nature, frequency and severity of the adverse reactions were investigated and documented. The incidence of acute adverse reactions to intravenous gadolinium-based contrast media was 0.48% (45 patients with 46 adverse reactions). The severity of these adverse reactions were 96% mild, 2% moderate (one patient developed shortness of breath that required oxygen supplementation and intravenous steroidal management) and 2% severe (one patient developed an anaphylactoid reaction, but successfully recovered through timely resuscitation). No patients were recorded as having contrast extravasation and none died as a result of any adverse reaction. Among the 45 patients who developed adverse reactions, three patients (6.7%) had prior adverse reactions to iodinated contrast media, three (6.7%) had prior reactions to a different gadolinium-based contrast agent, one (2%) had asthma and nine (20%) had a history of drug/food allergy. Overall, 41% of the adverse reactions were not documented in the final MRI report or the clinical medical records. Gadolinium-based contrast media are safe and well tolerated by the vast majority of patients. In our study, the adverse reaction rate (0.48%) and the incidence of severe anaphylactoid reaction (0.01%) concur with those reported in the literature. Although most of the symptoms are mild and transient, these adverse reactions must be accurately documented and managed.

Acute Disease↗
PubMed2006

Subchondral insufficiency fracture of the femoral head.

Subchondral insufficiency fracture of the femoral head is a recently recognised entity. There are a few cases reported in Japanese and Caucasian patients but none in the Hong Kong population. The condition typically occurs in elderly females with osteoporosis. Acute hip pain is the usual presentation. The patient may have concomitant insufficiency fractures elsewhere. Magnetic resonance imaging is usually required to make the diagnosis. The prognosis of the condition is unknown. Reported complications include rapid collapse of the femoral head and coxopathy. Joint replacement should be considered if conservative management fails.

Aged↗
PubMed2005

InAs/GaAs quantum-dot saturable absorbers for diode-pumped passively Q-switched Nd-doped 1.3-microm lasers.

A low-loss semiconductor saturable absorber based on InAs/GaAs quantum dots was developed for Q switching of a diode-pumped Nd-doped laser operating at 1.3 microm. With an InAs/GaAs quantum-dot saturable absorber, a diode-pumped Nd:YVO4 laser at 1342 nm was achieved. With an incident pump power of 2.2 W, an average output power of 360 mW with a Q-switched pulse width of 90 ns at a pulse repetition rate of 770 kHz was obtained.

Journal Article↗
PubMed2005

Menstrual-like breakdown and apoptosis in human endometrial explants.

BACKGROUND: Apoptosis occurs in late secretory and menstrual human endometrium and is thought to play an important role in endometrial physiology. Menstrual-like breakdown has been observed in vitro in endometrial explants. The purpose of this study was to assess the role of apoptosis in menstrual-like breakdown in human endometrial explants. METHODS: Human endometrial tissue was obtained during the mid-secretory phase and cultured with or without estrogen and progesterone. The occurrence of breakdown was assessed by histology. Apoptosis was determined by gel electrophoresis for the detection of DNA fragmentation and by immunohistochemistry using the M30 CytoDEATH and anti-cleaved caspase-3 (CASP3) antibodies for the detection of caspase activity. Expression of BCL2 and BAX was quantified using real-time PCR analysis. RESULTS: Apoptosis occurred in human endometrial explants at all time-points studied. Cleaved CASP3 and M30 antigen expression increased in all explants, suggesting the involvement of CASP3 in the apoptosis. Low BCL2:BAX ratios were observed in all samples when compared with pre-culture controls. Estradiol and progesterone supplementation of the culture media reduced or eliminated menstrual-like breakdown but did not affect the degree of apoptosis observed. CONCLUSIONS: The apoptosis observed in endometrium during the late secretory phase and menstrual phase does not appear to be mechanistically related to the tissue breakdown but rather may be involved in the impending remodelling that occurs in the endometrium in the transition from secretory to proliferative phase following the menses.

Adult↗
PubMed2005

Insulin-like growth factor binding protein-3 (IGFBP-3) localizes to and modulates proliferative epidermal keratinocytes in vivo.

BACKGROUND: The colocalization of insulin-like growth factor binding protein-3 (IGFBP-3) and IGF-I receptor (IGF-IR) in the basal/germinative layer of the epidermis suggests a key role in modulating epidermal homeostasis. OBJECTIVES: We aimed to clarify both the specific cellular localization and the effect of excess epidermal IGFBP-3 on keratinocyte proliferation. METHODS: (i) Total RNA was isolated from fluorescence-activated cell sorted basal human keratinocyte subtypes [keratinocyte stem cells, transit amplifying keratinocytes (TA), postmitotic differentiating keratinocytes (PMD)], and real-time polymerase chain reaction analysis was used to determine the abundance of IGFBP-3 and IGF-IR mRNAs. (ii) An IGFBP-3 transgenic mouse model was then used to assess the effect of excess epidermal IGFBP-3 on keratinocyte proliferation. Excess epidermal IGFBP-3 mRNA and protein was determined by in situ hybridization and immunohistochemistry, respectively. RESULTS: (i) The highest levels of IGFBP-3 mRNA were detected in TA keratinocytes, in contrast to IGF-IR mRNA levels which were highest in PMD keratinocytes. (ii) Elevated human IGFBP-3 mRNA and protein was confirmed in the epidermis of skin derived from transgenic mice. Excess IGFBP-3 reduced the relative percentage of proliferative keratinocytes (Ki67 positive) irrespective of skin location (belly, back and tail). Thus, in the epidermis, IGFBP-3 mRNA is highly expressed by proliferative keratinocytes (TA) and overexpression of IGFBP-3 inhibits keratinocyte proliferation. CONCLUSIONS: We conclude that in vivo IGFBP-3 ensures epidermal homeostasis via downregulation of keratinocyte proliferation, and thus modulates the early stages of keratinocyte differentiation.

Adult↗
PubMed2004

Effects of kava (Kava-kava, 'Awa, Yaqona, Piper methysticum) on c-DNA-expressed cytochrome P450 enzymes and human cryopreserved hepatocytes.

The effects of the herbal product kava (Kava kava, 'Awa, Yaqona, Piper methysticum) on human P450 isoforms were studied in vitro using both cDNA-expressed human enzymes and cryopreserved human hepatocytes. Increasing concentrations of an ethanolic extract of dried kava root and three purified kava lactones (methysticin, desmethoxyyangonin, and yangonin) were tested for their ability to inhibit the catalytic activity of a panel of P450 isoforms (1A2, 2A6, 2C9, C2C19, 2D6, 2E1, and 3A4) present as c-DNA expressed-enzymes and in previously cryopreserved human hepatocytes. In addition, the test compounds' effect on hepatocyte viability was evaluated by measuring cellular ATP content. In both models, the kava extract and the three kava lactones were found to be potent inhibitors of CYPs 1A2, 2C9, 2C19, 2E1, and 3A4 with IC50 values of approximately 10 microM. The test compounds were also moderately cytotoxic to human hepatocytes (EC50 values of approximately 50 microM). Methysticin was the most potent enzyme inhibitor as well as the most cytotoxic, followed by (in order of potency:) the kava root extract, desmethoxyyangonin, and yangonin. Our results suggest that the drug interaction and hepatotoxic potential of kava should be further investigated.

Cryopreservation↗
PubMed2004

Eosinophilia and symptomatic pulmonary amyloidosis.

The case of a man with progressive breathlessness and pulmonary infiltration caused by AL amyloidosis associated with multiple myeloma is presented. There was a marked peripheral eosinophilia, which has not previously been described with amyloidosis.

Aged↗
PubMed2004

HRCT lung abnormalities are not a surrogate for exercise limitation in bronchiectasis.

In paediatric bronchiectasis, there has been limited work on the relationship between disease severity as assessed by exercise limitation and high resolution computed tomography (HRCT). An observational study was performed on 36 children who completed a questionnaire, physical examination, spirometry and sputum analysis, followed by a low dose of radiation protocol chest computed tomography (CT) scan and cycle ergometry incremental exercise test. A modified Bhalla score was used to score the HRCT abnormalities. The exercise variables used to assess functional status were heart rate, oxygen consumption, oxygen saturations and time of exercise. The results were compared with established normal paediatric values. The median (range) age of the children was 13 yrs (10.6-17.1). Age, sex, height, weight or pubertal status were equally distributed between the children with cystic fibrosis (CF) or non-CF bronchiectasis. The children with non-CF bronchiectasis had a lower median forced expiratory volume in one second % predicted than the children with CF (69% versus 76%, respectively). The distribution of lung disease differed between the two groups. The children with CF bronchiectasis had predominantly right upper lobe disease, and scored higher for the presence and extent of bronchiectasis. Otherwise, there was no statistical difference in the overall CT score or the individual CT parameters between the groups. There was evidence of exercise limitation in both CF and non-CF bronchiectasis compared to normal children. No consistent relationships were identified between the lung function parameters, HRCT findings or exercise parameters in either disease group. In this study, high resolution computed tomography features were not found to be markers of exercise capacity. As spirometry, high resolution computed tomography features and exercise testing give different information in children with cystic fibrosis and non-cystic fibrosis bronchiectasis, the current authors suggest all three may be required for the comprehensive assessment of respiratory status.

Adolescent↗