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Biomedical subjects

Y Hao

Publications and source records attributed to Y Hao.

At least 91 records · Page 5Linked to original sources
PubMed1997

Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa.

Patients with retinitis pigmentosa (RP) typically develop night blindness early in life due to loss of rod photoreceptors. The remaining cone photoreceptors are the mainstay of their vision; however, over years or decades, these cones slowly degenerate, leading to blindness. We created transgenic pigs that express a mutated rhodopsin gene (Pro347Leu). Like RP patients with the same mutation, these pigs have early and severe rod loss; initially their cones are relatively spared, but these surviving cones slowly degenerate. By age 20 months, there is only a single layer of morphologically abnormal cones and the cone electroretinogram is markedly reduced. Given the strong similarities in phenotype to that of RP patients, these transgenic pigs will provide a large animal model for study of the protracted phase of cone degeneration found in RP and for preclinical treatment trials.

Animals↗
PubMed1997

Quality of life following bone marrow transplantation: a comparison of patient reports with population norms.

All surviving patients who had received an allogeneic bone marrow transplant at the Princess Margaret Hospital were asked to participate in a health-related quality of life (HQL) study using the Medical Outcomes Survey-Short Form 36 (MOS SF-36), the Satisfaction with Life Domains Scale-Bone Marrow Transplantation (SLDS-BMT) and a current symptoms checklist. The main objective was to compare the health status of BMT survivors with age-adjusted population norms. Of the 251 patients contacted, 93% returned questionnaires. The median follow-up after BMT was 40 months, ranging from 1-253 months. On average, survivors had some diminished HQL relative to the health status of the population in general. Time since transplant had a significant influence on HQL; those less than 3 years from transplant experienced considerable impairment while those who had survived beyond this point were indistinguishable from the normal population in most domains and significantly better in certain psychosocial aspects of health. Many patients still reported symptoms months after BMT; some were mildly affected while others experienced more troublesome symptoms. However, 81% of patients were satisfied with the HQL outcome that they had achieved and 94% would recommend a transplant for someone in similar circumstances.

Adult↗
PubMed1997

High-affinity CCK-A receptors on the vagus nerve mediate CCK-stimulated pancreatic secretion in rats.

Cholecystokinin (CCK) receptors are found on vagal afferent fibers. In pancreatic acini, CCK receptors exist in high- and low-affinity states. The aim of this study was to identify the vagal CCK-A receptor affinity state that mediates the effect of CCK on pancreatic protein secretion. Using a rat model with a pancreatic-biliary cannula, we studied the effects of CCK-JMV-180 on exocrine pancreatic function. CCK-JMV-180 acts as an agonist on high-affinity CCK receptors and as an antagonist on low-affinity CCK receptors. Infusion of CCK-JMV-180 (22-88 micrograms.kg-1.h-1) caused dose-dependent increases in pancreatic protein secretion, which were blocked by the CCK-A receptor antagonist L-364,718. Acute vagotomy in anesthetized rats and perivagal application of capsaicin in conscious rats abolished pancreatic responses to CCK-JMV-180 at 22 and 44 micrograms.kg-1.h-1. CCK-JMV-180 did not reduce pancreatic responses to CCK octapeptide infusion at 20 and 40 pmol.kg-1.h-1. To demonstrate that endogenously released CCK also acts on high-affinity CCK-A receptors, we showed that in conscious rats intraduodenal infusion of 18% casein produced a threefold increase in protein secretion and elevated plasma CCK levels from 0.7 to 8.4 pM. Infusion of CCK-JMV-180 at 44 micrograms.kg-1.h-1 failed to inhibit pancreatic responses to casein. In separate studies, perivagal application of 1% capsaicin inhibited 95% and 90% of the pancreatic responses to casein and casein combined with intravenous CCK-JMV-180, respectively. The neurotoxic effect of capsaicin on small-diameter sensory vagal fibers was verified by immunohistochemical and retrograde tracing studies. In conclusion, we demonstrated that in contrast to their effect on satiety, which is mediated by vagal low-affinity CCK-A receptors, exogenous CCK and endogenous CCK under physiological conditions act through high-affinity CCK-A receptors to mediate pancreatic protein secretion. These findings suggest that different affinity states of the vagal CCK receptors mediate different digestive functions.

Animals↗
PubMed1997

[Detection of ras gene mutation in various stages of gastric cancer by PCR/RFLP SSCP and DNA sequencing].

Investigate mutation of ras gene family in various stage of gastric cancer in China. PCR-RFLP, PCR-SSCP and PCR-DNA sequencing were used to detect mutation rates of H-ras, K-ras and N-ras gene. Mutation rates of H-ras at 12 codon in metaplasia, atypical hyperplasia, and progressive gastric cancer is 16.7% (6/36), 31.2% (15/48), 34.7% (25/72), respectively. In groups of superficial gastritis and normal control, no mutation were found. Mutations of H-ras 61 codon and N-ras 12 codon in various groups were the same as normal. Only 2 cases of K-ras 12 codon mutation were detected in gastric cancer by PCR-SSCP, but it was not identified by DNA sequencing. It may be of polymorphism. All H-ras 12 codon mutation were G-->T mutation. There are significant difference between groups of metaplasia, dysplasia, and gastric carcinoma comparing with group of normal control (P < 0.05, P < 0.01, P < 0.01). H-ras 12 codon mutation maybe an early event and maybe play important role in gastric carcinogenesis. Although K-ras mutation rate is high in colon cancer and leukemia it seemed to be relationship with gastric cancer. High frequency of H-ras 12 codon mutation maybe the characteristic of gastric cancer and associate with high incidence of gastric cancer in China. Three methods used in this experiment were compared that SSCP method is more sensitive than RFLP and cold SSCP is simpler and likely to be used in clinic.

Gastric Mucosa↗
PubMed1997

[Effects of IFN-alpha on the expressions of perforin and granzymes in IL-2 activated lymphocytes].

OBJECTIVE: To study the effect of IFN-alpha on the expressions of perforin and granzymes in IL-2-activated-lymphocytes. METHODS: NK and LAK activities were assayed by 4 hour standard 51Cr release test, the activity of perforin was detected by hemolysis method, expression of granzyme B was measured by ABC immunohistological method, expression of granzyme A was measured by BLT method. RESULTS: IFN-alpha significantly augmented the activities of NK and LAK in IL-2 activated peripheral blood lymphocytes (PBL) after 1 day culture. Perforin activity in lymphocytes was increased after 1 day exposure to IL-2 or IFN-alpha, and was enhanced when exposed to the combination of IL-2 and IFN-alpha. After 3 day culture, the perforin activity remained high in lymphocytes activated by IL-2 alone or in combination with IFN-alpha, while declined to control level in IFN-alpha exposed group. IL-2 and IFN-alpha alone or in combination had no effect on expression of granzyme A and B. CONCLUSION: IFN-alpha enhances the cytotoxicity of lymphocytes activated by IL-2. The mechanism might be that IFN-alpha upregulates the perforin expression.

Gene Expression Regulation↗
PubMed1997

[Preliminary study on oncogene MDM2 in acute leukemias].

OBJECTIVE: To explore the causes of MDM2 gene overexpression. METHODS: The amplification and overexpression of MDM2 gene in 41 acute leukemia patients and two leukemic cell lines (K051 and HL60) were studied by using Southern blot, dot hybridyzation and RT-PCR techniques. RESULTS: Overexpression of MDM2 gene was found in 51.2% (21/41) of the patients and HL60 cell line, but no amplification of the gene was found in all the patients and the two cell lines. CONCLUSION: The level of MDM2 gene expression was related to the prognoses of the patients but not to FAB subtypes of acute leukemias.

Actins↗
PubMed1997

[Clonal analysis of blood cells using X-linked HUMARA gene polymorphism].

OBJECTIVE: To explore the method for clonal analysis of blood cells. METHODS: Thirty female AML patients and 20 normal female subjects were analysed by the analysis of X-linked HUMARA gene polymorphism and methylation pattern. RESULTS: The heterozygote rate of HUMARA gene in Chinese women was 88% and the gene had a stable methylation pattern. Out of 20 control females, 17 were heterozygotes and among them 15 were polyclonal, 2 (11.8%) showed skewed X-inactivation. All heterozygote AML were clonal hematopoiesis. CONCLUSION: HUMARA gene polymorphism is a good marker for clonality analysis of blood cells.

Adult↗
PubMed1997

[Study on the immunophenotype of myeloid cells in myelodysplastic syndromes and its clinical implications].

OBJECTIVE: To explore the immunophenotype of myeloid cells in myelodysplastic syndromes and its clinical implications. METHODS: A panel of monoclonal antibodies was used to detect CD13, CD33, CD15 and CD14 on the membrane surfaces of myeloid cells in the bone marrow from 51 patients with myelodysplastic syndromes (MDS), 21 with aplastic anemia (AA), 21 with paroxysmal nocturnal hemoglobinuria (PNH), and 15 normal subjects, by immunoenzymatic assay. The morphology and chromosome karyotype of bone marrow cells of MDS patients were also examined. RESULTS: CD14+ cells, CD13+ cells and CD33+ cells in the bone marrow were more in MDS patients than in normal controls, AA patients and PNH patients. CD15+ cells in the bone marrow were less in MDS patients than in normal controls. The percentages of CD14, CD13 and CD33 positive cells in the bone marrow of MDS patients were related to the percentage of myeloblast, the chromosomal aberrations and the response to treatment. CONCLUSION: There was an immunophenotypic misexpression of myeloid cells in MDS patients. Immunophenotype analysis of myeloid cells might be useful for the diagnosis and directing treatment in MDS patients.

Adolescent↗
PubMed1997

[Study on T lymphocyte recognition of tumor antigens on autologous CML cells].

OBJECTIVE: To investigate the existence of cytotoxic precursor cells in previously untreated or remissive chronic myelogenous leukemia(CML) patients,and identify their phenotypical and functional characteristics. METHODS: Bone marrow or peripheral blood mononuclear cells from CML patients were stimulated with autologous CML cells by using mixed lymphocyte tumor cell coculture. RESULTS: A kind of cytotoxic T lymphocytes could be generated from bone marrow or peripheral blood of CML patients. These T cells showed differential cytotoxicities against autologous and allogeneic CML cells and no activity to autologous and allogeneic normal bone marrow cells. They also exhibited no inhibitive effect on CFU-GM yields. LAK cells had no effect on autologous CML cells, but showed intensive cytotoxic activity to allogeneic CML cells. The T lymphocytes obtained were CD3+ CD56+ non-MHC restricted or CD3+ CD56- MHC restricted. HLA-DR and CD25 were expressed in a significantly larger proportion of T lymphocytes stimulated with autologous CML cells than those not stimulated. The T lymphocytes showed low proliferative response to autologous CML cell stimulation and no or least response to allogeneic CML cells, they showed also no response to EB virus-transformed autologous B cells(obtained in remission) pulsed with peptides corresponding to the BCR-ABL joining region. CONCLUSION: There is probably a common tumor antigen among CMLs, this leukemia-specific antigen can be recognized by T cells,and it shows no indication to be a p210 fusion sequence.

Amino Acid Sequence↗
PubMed1997

[The killing effect of IL-2 and IFN-alpha activated bone marrow on K562 leukemic cell].

OBJECTIVE: To evaluate the killing effect of IL-2 and IFN-alpha activated bone marrow cells on K562 cells. METHODS: Semi-solid colony assay was used. RESULTS: Bone marrow from leukemia patients in remission was activated in vitro with IL-2 for 3 days. The activated bone marrow (ABM) displayed killing effects of 0.31 approximately 2.30 logs on K562 cells, this killing effects was further increased to 0. 30 approximately > 3.15 logs when IFN-alpha added with IL-2 to the marrow for activation. IL-2 alone or in combination with IFN-alpha showed no inhibition of CFU-GM and K562 cells. Compared with IL-2 or IFN-alpha alone, the combination of the two cytokines could more effectively maintain the killing effect of ABM on leukemic cells. CONCLUSION: IFN-alpha can augment the purging effect of IL-2 ABM and combination of the two cytokines can effectively maintain the cytotoxicity of ABM.

Bone Marrow Cells↗
PubMed1997

A pathologic study of degeneration of the rod and cone populations of the rhodopsin Pro347Leu transgenic pigs.

PURPOSE: Transgenic pigs with rhodopsin (Pro347Leu) mutation exhibited rod-cone degeneration. We compared the pathologic characteristics of the rod degeneration versus those of the cone cells. METHODS: The posterior and peripheral retinas of these transgenic pigs of age 4, 6, 8, 12, 24 and 33 weeks and normal pigs of age 4 and 8 weeks were studied by light and EM and morphometry. RESULTS: The pathologic changes observed in the posterior and peripheral retinas of the transgenic pigs could be conveniently described in 3 phases: I) an initial phase of rapid and extensive degeneration of the rod cells in the first 6 weeks of age; II) an acute phase of cone cell degeneration involving approximately half of the population and lingering rod degeneration in the 6 to 12 weeks of age; and III) a partial cone recovery to be followed by a chronic degenerative phase of the remaining cones cells from 12 to 33 weeks of age. CONCLUSION: Our study showed that the degenerative changes of rod cells could be differentiated from those of the cone cells. Cone and rod populations degenerated along different time schedule with different pathologic features. Hence, treatment for retinitis pigmentosa might vary with the different stages of the disease.

Animals↗
PubMed1996

Gadolinium(III) texaphyrin: a tumor selective radiation sensitizer that is detectable by MRI.

Gadolinium(III) texaphyrin (Gd-tex2+) is representative of a new class of radiation sensitizers detectable by magnetic resonance imaging (MRI). This porphyrin-like complex has a high electron affinity [E1/2 (red.) approximately = -0.08 V versus normal hydrogen electrode] and forms a long-lived pi-radical cation upon exposure to hydrated electrons, reducing ketyl radicals, or superoxide ions. Consistent with these chemical findings, Gd-tex2+ was found to be an efficient radiation sensitizer in studies carried out with HT29 cells in in vitro as well as in in vivo single and multifraction irradiation studies with a murine mammary carcinoma model. Selective localization of Gd-tex2+ in tumors was confirmed by MRI scanning.

Animals↗
PubMed1996

The absence of an adverse effect of prolongation of radiation treatment of primary rectal adenocarcinoma.

Many reports have shown a deleterious effect from the prolongation of radiation treatment duration on local control of squamous cell carcinomas in a variety of sites. To study whether a similar effect was found in adenocarcinoma of the rectum, a retrospective review was performed of 353 patients treated by external beam radiation therapy for primary adenocarcinoma of the rectum. At 4 years, the local control rate for mobile tumours was 25 percent; for fixed tumours it was 7 percent. By multiple Cox regression analysis, the only factor statistically significant for local control was tumour fixation (P=0.02). Neither treatment length (P=0.44), nor the presence of an interruption in treatment (P=0.41) was significant. The possible explanations for these observations are discussed.

Adenocarcinoma↗
PubMed1996

Targeting of glycoprotein I (gE) of varicella-zoster virus to the trans-Golgi network by an AYRV sequence and an acidic amino acid-rich patch in the cytosolic domain of the molecule.

Previous studies suggested that varicella-zoster virus (VZV) envelope glycoproteins (gps) are selectively transported to the trans-Golgi network (TGN) and that the cytosolic domain of gpI (gE) targets it to the TGN. To identify targeting signals in the gpI cytosolic domain, intracellular protein trafficking was studied in transfected cells expressing chimeric proteins in which a full-length or mutated gpI cytosolic domain was fused to the gpI transmembrane domain and interleukin-2 receptor (tac) ectodomain. Expressed protein was visualized with antibodies to tac. A targeting sequence (AYRV) and a second, acidic amino acid-rich region of the gpI cytosolic domain (putative signal patch) were each sufficient to cause expressed protein to colocalize with TGN markers. This targeting was lost when the tyrosine of the AYRV sequence was replaced with glycine or lysine, when arginine was replaced with glutamic acid, or when valine was substituted with lysine. In contrast, tyrosine could be replaced by phenylalanine and valine could be substituted with leucine. Mutation of alanine to aspartic acid or deletion of alanine abolished TGN targeting. Exposure of transfected cells to antibodies to the tac ectodomain revealed that the TCN targeting of expressed tac-gpI chimeric proteins occurred as a result of selective retrieval from the plasmalemma. These data suggest that the AYRV sequence and a second signaling patch in the cytosolic domain of gpI are responsible for its targeting to the TGN. The observations also support the hypothesis that the TGN plays a critical role in the envelopment of VZV.

Amino Acid Sequence↗
PubMed1996

[Changes in hematoporphyrin in patients with gastric and hepatic carcinoma and their clinical significance].

The fluorescence spectroscopy of porphyrin molecule in blood was determined with photoluminescence fluorescence spectroscope in 139 patients with gastric carcinoma, 76 with hepatic carcinoma, 110 with gastric ulcer and chronic gastritis, 168 with liver cirrhosis and 33 normals as controls. The results showed that the peaks of Zinc porphyrin and protoporphyrin in patients with cancer were significantly higher than those in patients with benign disease, the peak of protoporphyrin being two to three times higher in the former groups of patients than that in the latter (P < 0.01). Protoporphyrin could be used as a marker to screen and diagnose gastric and hepatic carcinoma.

Biomarkers, Tumor↗
PubMed1996

[Promotion of c-fos oncogene expression in cultured rabbit lens epithelial cells by macrophages].

OBJECTIVE: This study was designed to test the hypothesis that inflammatory cells deposited on the surface of implanted intraocular lens stimulate the proliferation of residual lens epithelial cells. METHODS: Immunocytochemical ABC methods with purified anti-human Fos protein serum antibody was used to stain the cultured rabbit lens epithelial cells incubated with rabbit macrophages and macrophage-conditioned medium (MCM). RESULTS: The lens epithelial cell growth was faster in the cultures with macrophages and MCM than in the controls. Fos protein positive staining was found in the nuclei of epithelial cells cultured with macrophages for 4 hours, and of the cells with MCM for one hour; whereas the staining was negative in the cells of control cultures. CONCLUSION: Macrophages promote c-fos oncogene expression in the lens epithelial cells, that might be mediated by bioactive factors secreted by macrophages.

Animals↗
PubMed1996

Relationship between some humoral factors and left ventricular hypertrophy in essential hypertension.

OBJECTIVE: To evaluate the relationship between certain humoral factors and left ventricular hypertrophy (LVH) in essential hypertension. PATIENTS AND METHODS: 62 essential hypertension (EH) patients (32 men, 30 women; mean age, 55 years) and 20 normotensive healthy subjects (10 men, 10 women: mean age, 52 years) were studied. EH patients were divided into LVH group and non-LVH group by echocardiography. After an overnight fast, blood samples were taken for the determination of parathyroid hormone (PTH), angiotensin II (ATII) and aldosterone (ALD) by radioimmunoassay. RESULTS: There was a significant difference in PTH. AT II and ALD between the EH group and control group. Furthermore, in LVH group PTH, ATII and ALD elevated significantly as compared with non-LVH group. In addition, we found that LVMI (left ventricular mass index) correlated with ATII (r = 0.342, P < 0.01) and ALD (r = 0.356, P < 0.01). There was a more significant correlation between LVMI and PTH (r = 0.422, P < 0.0025). CONCLUSIONS: Some humoral factors are important determinants of LV mass. Besides the reninangiotensin-aldosterone system, PTH might play an important role in cardiac hypertrophy.

Aldosterone↗