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Biomedical subjects

L Y Guo

Publications and source records attributed to L Y Guo.

13 recordsLinked to original sources

The Wilms' tumor gene product WT1 mediates the down-regulation of the rat epidermal growth factor receptor by nerve growth factor in PC12 cells.

Recently, we characterized the rat epidermal growth factor receptor (EGFR) promoter and demonstrated that TCC repeat sequences are required for the down-regulation of EGFR by nerve growth factor (NGF) in PC12 cells. In this study, we report that the Wilms' tumor gene product WT1, a zinc finger transcription factor, is able to enhance the activity of the rat EGFR promoter in cotransfection assays. Gel mobility shift assays demonstrate that WT1 binds to the TCC repeat sequences of the rat EGFR promoter. Overexpression of WT1 resulted in up-regulation of the expression levels of endogenous EGFR in PC12 cells. Interestingly, NGF down-regulated the expression levels of WT1 and EGFR in PC12 cells, but not in the p140(trk)-deficient variant PC12nnr5 cells or in cells expressing either dominant-negative Ras or dominant-negative Src. Most importantly, we evaluated the inhibitory effect of antisense WT1 RNA on EGFR expression, and we found that antisense WT1 RNA could substantially reduce EGFR repression in either histochemical staining study or immunoblot analysis. These results indicate that NGF-induced down-regulation of the EGFR in PC12 cells is mediated through WT1 and that WT1 may play an important role in the differentiation of nerve cells.

Animals↗

Cloning and characterization of the promoter region of the rat epidermal growth factor receptor gene and its transcriptional regulation by nerve growth factor in PC12 cells.

Our previous studies have shown that treatment of PC12 cells with nerve growth factor (NGF) causes a profound down-regulation of the epidermal growth factor receptor (EGFR) mRNA and protein. Further, the NGF-induced down-regulation of the EGFR is under transcriptional control. To elucidate the molecular mechanism of this down-regulation we have cloned a 2.7-kilobase sequence from the promoter region of the rat EGFR from a rat P1 library. Six transcriptional start sites were identified by 5'-rapid amplification of cDNA ends and primer extension. Sequence analysis showed a 62% overall homology with the human EGFR promoter region. To investigate its transcription, 1.1 kilobases of the 5'-flanking sequence were fused to a luciferase reporter gene. This sequence exhibited functional promoter activity in transient transfection experiments with PC12, C6, and CV-1 cells. Treatment of PC12 cells with NGF inhibited promoter activity. By transfection of promoter deletion constructs, a silencer element was found between nucleotides -260 and -181, and TCC repeat sequences appeared to be at least partially responsible for the down-regulation of the EGFR by NGF. Supportive evidence for the relevance of this sequence was obtained from gel mobility shift assays and by transfection of TCC mutation constructs. Our results demonstrate that TCC repeat sequences are required for the down-regulation of rat EGFR by NGF in PC12 cells and may lead to the identification of the NGF-responsive transcription factors.

Animals↗

Common abnormal kinetic patterns of the knee in gait in spastic diplegia of cerebral palsy.

We studied the kinetic characteristics of the knee in patients with spastic diplegia. Twenty three children with spastic diplegia were recruited and had their 46 limbs categorised into the following four groups: jump (n=7), crouch (n=8), recurvatum (n=14) and mild (n=17). In the crouch pattern, the patients usually had a larger and longer lasting internal knee extensor moments in stance suggesting that rectus femoris had a relatively high activation. In the recurvatum pattern, the internal knee flexor moment was large and long lasting in stance. The biceps femoris showed less activity on EMG although the knee flexor moment was large and we concluded that the soft tissue behind the knee joint provided this flexor moment. In the jump knee pattern there was abnormal power generation at the knee and ankle joints in initial stance, which did not contribute to normal progression but aided upward body motion. In the mild group the kinetic data was similar to that seen in normal children. Knowledge of kinetic patterns in these patients may help in their subsequent management.

Ankle Joint↗

[Characteristics and effect of allergic rhinitis in aircrew on flight].

OBJECTIVE: To observe the characteristics of allergic rhinitis in aircrew and its effect on flight. METHOD: Case studies of allergic rhinitis were made in 32 aircrew. RESULT: There were 20 cases of perennial allergic rhinitis and 12 cases of seasonal allergic rhinitis in 32 aircrew. Twenty-six cases are still in a qualified position to continue their flying job and the other six cases were permanently grounded. CONCLUSION: Allergic rhinitis in aircrew may affect the flying in aviation or space flight and the flying in aviation or space may induce or aggravate allergic rhinitis.

Adult↗

[Sensorineural deafness and aerospace flight].

OBJECTIVE: To probe the relations between sensorineural deafness and flying in aviation or space. METHOD: Case studies of sensorineural deafness were made in 36 pilots. RESULT: Unilateral deafness (n=15) and bilateral deafness (n=21) were found in 36 pilots, with mild deafness (n=9), moderate deafness (n=37) and severe deafness (n=11) in 57 ears. 19 cases were permanently grounded and 17 cases were still in a qualified position to continue their flying job. CONCLUSION: Sensorineural deafness may hazard the flying in aviation or space, meanwhile the flying in aviation or space may lead to or aggravate sensorineural deafness.

Adult↗

Cloning of a cDNA encoding a nerve growth factor precursor from the Agkistrodon halys Pallas.

Based on the high conservation in the 5' and 3' untranslated regions of NGF cDNAs, oligonucleotides complementary to all these known sequences were synthesized. By RT-PCR, we successfully isolated the complementary DNA encoding NGF precursor from the Agkistrodon halys Pallas (a Chinese snake strain). The nucleotide sequence which presents 90.5%, 88.6% and 63.4% homology to that of Krait Bungarus multicinctus, cobra and human NGF respectively, encoded a prepro-NGF molecule with 241 amino acids and a mature NGF molecule with 119 amino acids. The NGF cDNA inserts were subcloned into pCDNA3 expression vector and then transfected into COS-7 cells. The supernatant of the transfected cells turned out NGF biological activity as assayed by the survival rate of PC12 pheochromocytoma cells.

Agkistrodon↗

[The characteristics of Meniere's disease in aircrew].

OBJECTIVE: To study the characteristics of Meniere's disease in aircrew and its possible influence on space flight. METHOD: Case studies of Meniere's disease were carried out in 22 pilots. RESULT: There were vertigo (n=22), tinnitus (n=21), abnormal hearing (n=19) and abnormal vestibular function (n=11) in 22 pilots. CONCLUSION: Meniere's disease may hazard the flying in aviation or space and flying may further damage the inner ears of patients with Meniere's disease.

Aerospace Medicine↗

Identification of a serine protease with nerve growth promoting activity from snake venom.

A new protein with nerve growth promoting activity was purified from the crude venom of the Agkistrodon halys Pallas, a Chinese snake. Its amino-terminal sequence unexpectedly showed high homology with serine proteases, suggesting that it is a new member of the serine protease family. It also cross-reacted with antibodies against thrombin-like enzyme and possessed weak arginine esterase activity, amounting to about 3% of the activity of trypsin. However, its nerve growth promoting activity was comparable to that of nerve growth factor (NGF). It was named NGF-like protease (NLP). Northern blot analysis further demonstrated different patterns of induction of c-myc, vgf and trkA mRNA transcription in PC12 pheochromocytoma cells treated with NGF and NLP, respectively. These data suggested that NLP represents a novel potent neurotrophic factor.

Agkistrodon↗

Development of anti-p185HER2 immunoliposomes for cancer therapy.

The product of the HER2 protooncogene, p185HER2, represents an attractive target for cancer immunotherapies. We have prepared anti-p185HER2 immunoliposomes in which Fab' fragments of a humanized anti-p185HER2 monoclonal antibody with antiproliferative properties (rhuMAb-HER2) were conjugated to either conventional or sterically stabilized liposomes. These immunoliposomes bind specifically to p185HER2-overexpressing breast cancer cells (SK-BR-3 and BT-474). High-affinity binding of anti-p185HER2 immunoliposomes is comparable to that of free rhuMAbHER2-Fab' or the intact antibody. Empty immunoliposomes inhibit the culture growth of p185HER2-overexpressing breast cancer cells, and this antiproliferative effect is superior to that of free rhuMAbHER2-Fab', indicating that liposomal anchoring of these anti-p185HER2 Fab' fragments enhances their biological activity. Efficient internalization of anti-p185HER2 immunoliposomes, demonstrated by light and electron microscopy, occurs by receptor-mediated endocytosis via the coated pit pathway and also possibly by membrane fusion. Doxorubicin-loaded anti-p185HER2 immunoliposomes are markedly and specifically cytotoxic against p185HER2-overexpressing tumor cells in vitro. Anti-p185HER2 immunoliposomes administered in vivo in Scid mice bearing human breast tumor (BT-474) xenografts can deliver doxorubicin to tumors. These results indicate that anti-p185HER2 immunoliposomes are a promising therapeutic vehicle for the treatment of p185HER2-overexpressing human cancers.

Animals↗

[Clinical study on epidermal growth factor and its receptor in human gastric cancer].

We detect the expression of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) in 104 specimens of gastric cancer by avidin biotin-peroxides complex technique (ABC). The positive rates of EGF, EGFR and synchronous EGF and EGFR were 35.6%, 42.3%, 30.8% respectively. The positive expression of EGF and EGFR to gastric cancer tissue was inclined to occur in patients who were in advanced stages, of poorly-differentiated types, Borrmann III, IV types, scirrhous type, seroinvasive type or lymph node metastasic types. The survival rates at 1, 3, 5 years after gastrectomy in the patients with expression of EGF were significantly lower than the survival rates of the patients with negative expression (P < 0.05). The patients with synchronous expression of EGF and EGFR had the worst prognosis. After gastrectomy, all of them died within 4 years. It is indicated that EGF and EGFR could serve as biological indicators of gastric cancer malignancy and an index for evaluating, the prognosis of the patients with gastric cancer.

Adenocarcinoma↗

Two widely accessible media for growth and reproduction of phytophthora and pythium species.

Tomato agar and soybean agar were found to be comparable to or in some cases better than the popular V8 vegetable juice agar in supporting linear growth of Phytophthora cactorum, Phytophthora capsici, Phytophthora parasitica, Pythium aphanidermatum, and Pythium splendens; sporangium production of P. capsici, P. palmivora, and Pythium splendens; and oospore formation of P. cactorum, P. parasitica, Pythium aphanidermatum and Pythium splendens. These two media with readily accessible ingredients can be used to substitute for V8 juice agar in pathological and physiological studies of these two important groups of fungi in countries where V8 vegetable juice is not available or difficult to obtain.

Journal Article↗

Maloalcoholic fermentation by immobilized Schizosaccharomyces pombe.

Cells of Schizosaccharomyces pombe TMB 1138, which are capable of metabolizing-malate, was immobilized in calcium alginate gel to carry out maloalcoholic fermentation. Four milliliters of cell suspension containing about 2.0 X 10(7) cells were entrapped in 16 ml of sodium alginate solution in order to prepare 2% Na-alginate (w/v) gel bead. After activation by incubating at 28 degrees C for 24 h in grape juice, 300 beads of immobilized cells were inoculated into the fermentation medium. After fermentation was proceeded at 25 or 28 degrees C for 24 h by shaking, it could metabolize L-malate completely and the total acidity was also reduced. Under the same condition for batch fermentation, it was found that the utilization of L-malic acid was over 97% for the first 7 days in fermentation medium, 85% for the first 4 days in grape juice and 87% for the first 4 days in wine. Furthermore, for the continuous fermentation in wine, the conversion of L-malic acid reached 92% in 24 h and could be maintained at 75% in the following 9 days.

Alginates↗

A 2-D model of wheelchair propulsion.

PURPOSE: To illustrate the potential benefits of kinetic and kinematic models in the exploration of biomechanical studies as illustrated using a simple 2-D static optimization model of wheelchair propulsion. METHOD: A four-bar linkage analysis was used to determine sagittal plane motion through the range of wheelchair propulsion. Using anthropometric measures of wheelchair users, this analysis determined the angles of shoulder and elbow flexion/extension at a given point in the propulsion cycle. Maximal strength inputs for the model were collected from isokinetic measurements of shoulder and elbow moments. The torque inputs were given as functions of sagittal plane joint angles. Through selection of appropriate model performance criteria, optimization techniques determined shoulder and elbow torque contributions throughout the propulsion cycle. Variations in the model parameters of anterior-posterior (AP) seat position and handrim size went used to show potential of model to evaluate wheelchair configuration using the performance criteria of propulsive moment (Mo) and efficiency as defined by fractional effective force (FEF). RESULTS: The model was able to predict the magnitude and direction of force applied to the handrim from shoulder and elbow moments. These joint moments may be examined along with the generated wheelchair axle propulsion moment. While the model showed no significant changes in either Mo or FEF for AP seat changes, an increase in handrim size was shown to increase FEF. CONCLUSIONS: This model was able to simulate wheelchair propulsion and allow for performance analyses. The open nature of the model allowed for tweaking of the kinematic inputs to examine the sensitivity of such factors as seat position and handrim size in wheelchair propulsion. Strength inputs to the model may also be altered to study the potential effects of strength training or muscle weakness.

Biomechanical Phenomena↗