Biomedical subjects

Sha Liu

Publications and source records attributed to Sha Liu.

32 records · Page 2Linked to original sources

PubMed2004

[Immunogenicity analysis of HIV vaccine based on replicating vaccinia virus Tiantan vector].

OBJECTIVE: To investigate the immunogenicity of HIV vaccine vTKgpe based on Vaccinia Virus Tiantan vector in mice and rabbits. METHODS: Mice were inoculated with HIV vaccine vTKgpe by intramuscular (i.m.), intradermal (i.d.) or subcutaneous (s.c.) injections. Blood sample were collected every week, and then antibodies against HIV and vaccinia virus vector were detected. At week 4, some mice were killed and cellular immune responses were examined by flow cytometer. Additionally two rabbits were vaccinated subcutaneously, blood sample were tested as done with mice. RESULTS: In mice i.m. and s.c. groups, HIV specific antibodies emerged at week 2 and declined at week 4. Antibodies against vector elevated rapidly at week 4, and potentially affected HIV specific antibody detection. Cellular immune responses were only detected in s.c. group. Serum of rabbit showed that anti-HIV antibody appeared at week 2 and maintained for several weeks. CONCLUSION: Vaccine vTKgpe innoculated by i.m. and s.c routes inclined to induce humoral immune responses in mice, but in i.d. group, inclined to induce cellular immune responses. Response to the recombinant vaccinia virus was more sensitive in rabbit than in mice.

AIDS Vaccines↗

PubMed2004

[Cochlear implantation in patients with inner ear malformations].

OBJECTIVE: To describe clinical experiences with multi-channel cochlear implantation in patients with bilateral inner ear malformations. METHODS: Among 410 patients who received multi-channel cochlear implantations from 1996 to 2004 in Beijing Tongren Hospital, 82 patients were diagnosed with inner ear malformations and implanted. A retrospective analysis was performed about the surgical characteristics and mapping characteristics after implantation. RESULTS: (1) All patients had auditory sensations. (2) Gusher was more common than the normal cochlear implantation. (3) The electrodes were inserted in the "cochleostomy" in full length of 80 Patients, but 2 pairs of electrodes remained outside of "cochleostomy" in 2 patients. (4) No serious complications occurred after implantation. (5) The impedance of the electrodes, the T level and C level were similar with the normal cochlear implantation. The results had no significant difference in compare with normal cochlear group (P > 0. 05). (6) The abilities of speech discrimination and spoken language were improved through rehabilitation. CONCLUSIONS: The cochlear implantation can be performed safely in inner ear malformations. The outcome of hearing rehabilitation for patients with inner ear malformations are similar to those children with normal cochlear structure followed the multi-channel cochlear implantation.

Adolescent↗

PubMed2003

Design and synthesis of novel RXR-selective modulators with improved pharmacological profile.

New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were synthesized in an expedient and selective way. A subset of these compounds was evaluated for their metabolic properties (exposure in IRC male mice) and show a dramatic increase of exposure compared to our reference compound, 3 (LG101506).

Animals↗

PubMed2003

Design, synthesis, and structure-activity relationship studies of novel 6,7-locked-[7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta]-2,4,6-trienoic acids.

Retinoid X receptor:peroxisome proliferative-activated receptor (RXR:PPAR) heterodimers play a critical role in the regulation of glucose (RXR/PPARgamma) and lipid metabolism (RXR/PPARalpha). Previously, we described a concise structure-activity relationship study of selective RXR modulators possessing a (2E,4E,6Z)-3-methyl-7-(3,5-dialkyl-6-alkoxyphenyl)-octa-2,4,6-trienoic acid scaffold. These studies were focused on the 2-position alkoxy side chain. We describe here the design and synthesis of a novel series of RXR selective modulators possessing the same aromatic core structure with the addition of a ring locked 6-7-Z-olefin on the trienoic acid moiety. The synthesis and structure-activity relationship studies of these 6,7-locked cyclopentenyl, phenyl, thienyl, furan, and pyridine-trienoic acid derivatives is presented herein.

Alkenes↗

PubMed2003

[Cochlear implantation in patients with inner ear malformations, clinical analysis of 25 cases].

OBJECTIVE: To explore the clinical experience of multi-channel cochlear implantation in patients with bilateral inner ear malformations. METHOD: Multi-channel cochlear implantation was conducted among 180 patients from 1997 to 2001. Twenty-five of them, being with inner ear malformations, were given hearing and speech rehabilitation including sound detection, word discrimination, auditory comprehension and spoken language skill development. A follow-up lasting 4 - 24 months was conducted after the operation. A retrospective analysis was performed among these 25 patients to observe the surgical outcomes and mapping characteristics after surgery. RESULTS: (1) All patients restored their auditory sensations after the operation. (2) Stapedial gusher was found in 13 cases with inner ear malformations, especially those with Mondini malformation, much more frequently than among the patients with other malformations. (3) Most of the action electrodes were inserted in the "cochleostomy" in full length, only 2 pairs of them remained outside of the "cochleostomy". (4) No serious complications occurred after implantation. (5) The impedance of the electrodes, T level and C level were higher in the 25 cases than in the normal cochlear implantation, however, with the hearing similar hearing threshold. (6) After training, the abilities of speech discrimination and spoken language were improved in comparison with those before operation. CONCLUSION: The cochlear implantation can be performed safely in patients with bilateral inner ear malformations. The primary outcome of cochlear implantation in hearing rehabilitation is similar for both the patients with inner ear malformations and those with normal cochlear structure.

Adolescent↗

PubMed2003

[Two HLA-loci mismatched sibling cord blood transplantation in a severe beta-thalassemia patient].

Allogeneic hematopoietic stem cell transplantation is the only curative therapy for severe beta-thalassemia. This time, the experience of utilizing HLA 2-loci mismatched sibling cord blood transplantation (CBT) in a child with severe beta-thalassemia was firstly reported in our country. A 3-year-male patient had been diagnosed with severe beta-thalassemia at 6 months of age (HbF 86.6%, HbA1 1.7%, HbA2 1.7%, beta globin gene mutation CD17, A-->T/IVS-II-654, C-->T). The patient's HLA typing was A 24,11, B 58,35 and DRB1 03,15. During a subsequent maternal pregnancy. The prenatal diagnosis for thalassemia and prenatal HLA typing analysis were performed on 18 weeks of pregnancy. The results indicated that the male fetus was a heterozygote (beta globin gene mutation N/CD17, A-->T), HLA typing was A 24,11, B 58,51 and DRB1 03,12. 120 ml cord blood was collected at time of delivery, the total numbers of nucleated cells, CFU-GM and CD34(+) cells were 1.830 x 10(9), 16.653 x 10(5) and 3.11 x 10(6), respectively. A new conditioning regimen including: hypertransfusion, continuous i.v. desferrioxamine, busulfan, cyclophosphamide, antithymocyte globulin plus hydroxyurea and fludarabine. GVHD prophylaxis comprised cyclosporin A and mycophenolate mofetil. The viability of cord blood at the time infusion was 92%, The total numbers of nucleated cells, CFU-GM and CD34(+) cells in the transfused cord blood were 12.06 x 10(7)/kg, 1.098 x 10(5)/kg, and 2.04 x 10(6)/kg, respectively. Results showed that the patient's clinical course after cord blood transplantation was unremarkable. Acute GVHD grade I developed on day 15, methylprednisolone 2 mg/kg was given to cure. Neutrophil engraftment (ANC > 0.5 x 10(9)/L) on day 17, platelet engraftment (> 50 x 10(9)/L) on day 50. The patients became independent from red blood cell transfusion since day 80 (when his hemoglobin level kept > 12.5 g/L). His beta globin gene mutation and HLA typing were all the same as the donor's analyzed on day 60 and 200. There was also a switch in blood group from A pre-transplant to O post-transplant. It is concluded that the new conditioning and GVHD prophylaxis regimens allow a successful engraftment in this case. This observation may contribute in developing UCBT as an alternative when matched sibling donors are not available.

Child, Preschool↗

PubMed2003

[Cochlear implants in children with enlargement of vestibular aqueduct].

OBJECTIVE: To describe the clinical experiences with multi-channel cochlear implantation in the children with enlargement of vestibular aqueduct. METHOD: Fifteen patients were diagnosed with enlargement of vestibular aqueduct and received multi-channel cochlear implantation at Beijing Tongren Hospital. A cochleostomy was performed for all patients by a standard facial recess approach to anterior inferior to the round window niche. RESULTS: (1) Most of the electrodes were totally inserted in the cochlear, and gusher appeared in 6 implantations. (2) No serious complications occurred after implantation. (3) All patients have auditory sensations after implantations. (4) The hearing threshold in this series were similar to that of the normal cochlear implantation (the average threshold was 30 dB). (5) The rehabilitation concept was developed by Rehabilitation Research Center for Deaf Children in Beijing and Beijing Tongren Hospital. The training sessions included sound detection, word discrimination, auditory comprehension and spoken language skill development. The abilities of speech discrimination and spoken language were improved comparing with that of pre-operation. Two of the patients could go to the normal school after implantations. CONCLUSION: The outcome of hearing rehabilitation for children with enlargement of vestibular aqueduct were similar to those children with "normal" cochlear structure followed the multi-channel cochlear implantation.

Adolescent↗

PubMed2003

[Analysis of growth model in vestibular aqueduct during human fetal development].

OBJECTIVE: To characterize the growth of the developing vestibular aqueduct in order to gain a better understanding of the possible origins of enlarged vestibular aqueduct. METHODS: Serial sections from 32 temporal bones for every other week from human embryos ranging in age from 6 to 38 weeks were studied with 3DMed medical image analysis software. The internal, external aperture, midpoint diameter and length vestibular aqueduct were analyzed with regression analysis to obtain a growth curve. RESULTS: The internal aperture of vestibular aqueduct was began to form at 6 weeks' gestation. It grew to reach the posterior surface of the petrous bone in the posterior cranial fossa by 10 weeks' gestation. All width parameter mean value in our embryos nerve reached the maximum average width in the adult. Statistical analysis showed that the vestibular aqueduct grew in a nonlinear continuous fashion and instability trend throughout embryonic life, except length parameter. CONCLUSION: The vestibular aqueduct grows in a nonlinear fashion throughout embryonic life. The widest aqueduct measured in embryonic life does not reach the maximum average width in the adult. These results suggest that it would be possible for vestibular aqueduct to develop postnatally.

Anthropometry↗

PubMed2002

Phosphoenolpyruvate carboxykinase overexpression selectively attenuates insulin signaling and hepatic insulin sensitivity in transgenic mice.

The ability of insulin to suppress gluconeogenesis in type II diabetes mellitus is impaired; however, the cellular mechanisms for this insulin resistance remain poorly understood. To address this question, we generated transgenic (TG) mice overexpressing the phosphoenolpyruvate carboxykinase (PEPCK) gene under control of its own promoter. TG mice had increased basal hepatic glucose production (HGP), but normal levels of plasma free fatty acids (FFAs) and whole-body glucose disposal during a hyperinsulinemic-euglycemic clamp compared with wild-type controls. The steady-state levels of PEPCK and glucose-6-phosphatase mRNAs were elevated in livers of TG mice and were resistant to down-regulation by insulin. Conversely, GLUT2 and glucokinase mRNA levels were appropriately regulated by insulin, suggesting that insulin resistance is selective to gluconeogenic gene expression. Insulin-stimulated phosphorylation of the insulin receptor, insulin receptor substrate (IRS)-1, and associated phosphatidylinositol 3-kinase were normal in TG mice, whereas IRS-2 protein and phosphorylation were down-regulated compared with control mice. These results establish that a modest (2-fold) increase in PEPCK gene expression in vivo is sufficient to increase HGP without affecting FFA concentrations. Furthermore, these results demonstrate that PEPCK overexpression results in a metabolic pattern that increases glucose-6-phosphatase mRNA and results in a selective decrease in IRS-2 protein, decreased phosphatidylinositol 3-kinase activity, and reduced ability of insulin to suppress gluconeogenic gene expression. However, acute suppression of HGP and glycolytic gene expression remained intact, suggesting that FFA and/or IRS-1 signaling, in addition to reduced IRS-2, plays an important role in downstream insulin signal transduction pathways involved in control of gluconeogenesis and progression to type II diabetes mellitus.

Animals↗

PubMed2002

Cardiac myxoma and myxosarcoma: clinical experience and immunohistochemistry.

From January 1978 to February 1999, 120 patients (42 males and 78 females) with cardiac myxoma (115) or myxosarcoma (5) underwent surgical excision or biopsy. There were 5 early postoperative deaths (mortality, 4.2%). Seventy-three survivors were followed up for 0.75 to 20.25 years (mean, 9.42 years); they comprised 4 myxosarcoma patients who all had recurrence or metastasis, and 69 myxoma patients who had no evidence of recurrence or metastasis. Neither familial myxoma nor Carney complex was found. The 5 cases of myxosarcoma and 18 randomly selected cases of myxoma were evaluated for proliferative activity, metastatic potential, and oncogene products by immunohistochemistry. The expression of p53 and Bcl-2 was similar in both groups. Overexpression of proliferating cell nuclear antigen and low expression of nm23 in myxosarcoma are consistent with the high rate of recurrence and metastasis of this tumor. Surgical resection of sporadic myxoma is a safe and effective treatment with satisfactory early and long-term results. However, the prognosis of myxosarcoma is still disappointing. Regular echocardiography and chest radiography or computed tomography are necessary for early detection of recurrence or metastasis of myxosarcoma.

Adolescent↗

PubMed2002

Mechanism of selective retinoid X receptor agonist-induced hypothyroidism in the rat.

The retinoid X receptor (RXR) agonist bexarotene can cause clinically significant hypothyroidism in cutaneous T cell lymphoma patients. The mechanism by which the RXR agonist produces this effect is unclear. We have studied the impact of a selective RXR agonist (rexinoid), LG100268, on rat thyroid axis hormones and show that the acute phase of hypothyroidism is associated with reduced pituitary TSH secretion. A single oral administration of LG100268 to naive Sprague Dawley rats causes a rapid and statistically significant decline in TSH levels (apparent in 0.5-1 h). Total T(4) and T(3) levels decline more gradually, reaching statistical significance 24 h after treatment. Increasing doses of LG100268 produce greater suppression of thyroid axis hormones. To investigate the mechanism(s) mediating this suppression, we determined pituitary TSHbeta mRNA, TSH protein levels, and TRH-stimulated TSH secretion. Two hours after treatment, neither TSHbeta mRNA nor TSH protein levels were altered by LG100268. However, LG100268 treatment reduced the area under the curve for TRH-stimulated TSH secretion by 54%. We have identified an unexpected mechanism by which rexinoids induce hypothyroidism by acutely reducing TSH secretion from the anterior pituitary. This mechanism is independent of the rexinoid's previously demonstrated inhibition of TSHbeta gene transcription.

Animals↗

PubMed2002

A tailored therapy for the metabolic syndrome: the dual peroxisome proliferator-activated receptor-alpha/gamma agonist LY465608 ameliorates insulin resistance and diabetic hyperglycemia while improving cardiovascular risk factors in preclinical models.

A novel nonthiazolidinedione dual peroxisome proliferator- activated receptor (PPAR)-alpha/gamma agonist, LY465608, was designed to address the major metabolic disturbances of type 2 diabetes. LY465608 altered PPAR-responsive genes in liver and fat of db/db mice and dose-dependently lowered plasma glucose in hyperglycemic male Zucker diabetic fatty (ZDF) rats, with an ED(50) for glucose normalization of 3.8 mg small middle dot kg(-1) small middle dot day(-1). Metabolic improvements were associated with enhanced insulin sensitivity, as demonstrated in female obese Zucker (fa/fa) rats using both oral glucose tolerance tests and hyperinsulinemic-euglycemic clamps. Further characterization of LY465608 revealed metabolic changes distinct from a selective PPAR-gamma agonist, which were presumably due to the concomitant PPAR-alpha agonism, lower respiratory quotient, and less fat accumulation, despite a similar impact on glycemia in male ZDF rats. In addition to these alterations in diabetic and insulin-resistant animals, LY465608 dose-dependently elevated HDL cholesterol and lowered plasma triglycerides in human apolipoprotein A-I transgenic mice, demonstrating that this compound significantly improves primary cardiovascular risk factors. Overall, these studies demonstrate that LY465608 beneficially impacts multiple facets of type 2 diabetes and associated cardiovascular risk, including those facets involved in the development of micro- and macrovascular complications, which are the major sources for morbidity and mortality in these patients.

Animals↗

PubMed2002

[Related structures of the lateral sphenoid wall anatomy studies in CT and MRI].

OBJECTIVE: To study the anatomy of the Lateral Sphenoid Wall in CT and MRI in normal adults so as to provide a theoretical basis for imagine science. METHOD: High resolution CT in axial and coronal planes was conducted on 25 normal adults. MRI in axial and coronal planes, using SE T1 WI and FSE T2 WI was conducted on 20 volunteers. RESULT: 1. The pneumatisation of sphenoid sinus can be divided into two types: Pneumatisation of the sphenoid body and the one of sphenoid process. The former one can be subdivided into three categories: concha (2%), pre sellar (20%), sellar (78%). The latter can be subdivided into four categories: lesser wing (38%), greater wing (40%), pterygoid process (34%) and dorsum sellar (6%). 2. The thinnest part (< 1 mm) of the LSW is located at the inner wall of the optic nerve canal (96%), at the bony wall in the plane of sphenoethmoid recess (86%), the bony wall in the plane of the internal carotid artery (66%). 3. Over pneumatised sphenoid sinus could make the foramen rotumdum (64%) and pterygoid canal (44%) protrudes into the sphenoid cavity. CONCLUSION: Attention should be paid to the various mode of pneumatization around the optic nerve canal.

Adolescent↗

PubMed2002

[Comparison of neural response telemetry thresholds with behavioral T/C levels].

OBJECTIVE: To provide an objective method to estimate T-levels and C-levels using neural response telemetry (NRT) thresholds for children, from whom we can not get accurate responses because they are very young or have other disabilities, by comparing NRT thresholds and T/C levels. METHODS: Seventy patients implanted with the nucleus CI24M multiple cochlear implant system participated in this study. 329 electrodes were tested. The software used in this study was NRT 2.04. Monopolar stimulation mode was used during NRT threshold measurement. No. 3, 5, 10, 15, 20 electrodes were tested for each patient. The T-levels and C-levels were obtained at the same visit. RESULTS: 92.7% of all the tested electrodes recorded NRT responses. There were variations in the amplitudes and thresholds of NRT responses across subjects and electrodes. NRT thresholds fell within the different points of the MAP dynamic range. The mean of NRT thresholds was shown to fall between the mean of T-levels and C-levels. The NRT thresholds and T/C levels reduced from basal to apical ends of the cochlear. CONCLUSIONS: Considerable variability across subjects was noted. So it is difficult to estimate T-levels and C-levels accurately by testing only NRT thresholds only. NRT technology provides a new objective method for estimating T-levels and C-levels for children who are unable to cooperate with audiologists during mapping after operation. The new NRT technology should be improved in the future.

Adolescent↗