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Biomedical subjects

Y Hao

Publications and source records attributed to Y Hao.

At least 109 records · Page 6Linked to original sources

[New flexible open-loop anterior chamber lens in secondary implantation].

OBJECTIVE: To determine the efficacy of new flexible open-loop anterior chamber intraocular lens (AC IOL) in secondary implantation. METHOD: Secondary AG-IOL implantation in 35 eyes including 28 with traumatic cataract and 7 with senile cataract was performed 3 months to 2.5 years after primary cataract extraction. All patients were followed up for at least 6 months. RESULTS: Of the 35 eyes, 27 (77.1%) had a final visual acuity of 0.5 or better and 11 (31.4%) had 1.0 or better. CONCLUSION: New flexible open-loop AC IOL is safe and effective for secondary IOL implantation.

Adolescent↗

Altered cAMP levels in retinas from transgenic mice expressing a rhodopsin mutant.

Transgenic mice expressing the rhodopsin mutant Pro347Ser (Serine 6) display retinal degeneration through apoptosis that is characteristic of the disease retinitis pigmentosa. By 5 weeks after birth, these mice have lost approximately 35% of their photoreceptor cells. Retinas from these mice showed higher levels of cAMP compared to the levels in retinas of normal mice. Our studies provide evidence that elevated cAMP is common to the apoptotic process that occurs in retinitis pigmentosa. In addition, in vitro studies demonstrate no differences in the ability of the mutant and the wild-type rhodopsin to activate transducin, the rod cell G protein, to be phosphorylated by rhodopsin kinase or to bind arrestin. Mutants of rhodopsin, including Pro347Ser, are mistargeted to the rod inner segment, raising the possibility that rhodopsin triggers apoptosis through activation of signaling pathways not normally under its control.

Animals↗

Evidence for autoregulation of cholecystokinin secretion during diversion of bile pancreatic juice in rats.

BACKGROUND & AIMS: The mechanism regulating cholecystokinin (CCK) secretion during prolonged diversion of bile pancreatic juice (BPJ) is unknown. We examined the hypothesis that the decrease of plasma CCK levels after prolonged diversion of BPJ is mediated by an increase in plasma somatostatin levels evoked by hypercholecystokinemia and somatostatin in turn inhibits CCK-releasing peptide (CCK-RP) bioactivity and decreases plasma CCK levels. METHODS: Pancreatic secretion, plasma CCK levels, and somatostatin levels were monitored for 7 hours after diversion of BPJ in anesthetized rats. Secretion of CCK-RP bioactivity during diversion of BPJ was examined in the presence or absence of somatostatin. RESULTS: Diversion of BPJ for 2 hours caused a 13- and 2.5-fold increase in plasma CCK and somatostatin levels. The increase in somatostatin levels was blocked by the CCK antagonist L364,718. At 5 hours after diversion of BPJ, plasma CCK and somatostatin levels and luminal CCK-RP bioactivity decreased to basal levels. The decrease in plasma CCK levels was prevented by the administration of a specific somatostatin antagonist. We also showed that the stimulatory effect of the CCK-RP bioactivity was eliminated when the donor rat was pretreated with somatostatin. CONCLUSIONS: Autoregulation of CCK secretion occurs during the diversion of BPJ and this is mediated by somatostatin, which inhibits the secretion of CCK-RP bioactivity and decreases plasma CCK levels.

Analysis of Variance↗

Response of rat spinal cord to very small doses per fraction: lack of enhanced radiosensitivity.

Our previous work with rat spinal cord demonstrated that the linear quadratic (LQ) model based on data for large fraction sizes (alpha/beta of 2.4 Gy) failed to predict isoeffective doses between 1 and 2 Gy per fraction, and under-estimated the sparing effect of small doses per fraction given once daily. In contrast, data from mouse skin and kidney, and recent in vitro results revealed a paradoxical increase in radiosensitivity at below 1 Gy per fraction. To assess whether enhanced radiosensitivity is present in the spinal cord below 1 Gy per fraction, the rat spinal cord (C2-T2) was irradiated initially with three daily doses of 10.25 Gy (top-up doses representing 90% of tolerance), followed by graded single doses or fractionated doses in 1.5, 1.0, 0.8, 0.6 or 0.4 Gy fractions given once daily. To limit the overall treatment time to < or = 8 weeks, a small number of the 0.6- and 0.4-Gy fractions were given twice daily with an interfraction interval of 16 h. The end-point was forelimb paralysis secondary to white matter necrosis, confirmed histologically. The ED50 values, excluding the top-up doses, were 5.8, 10.6, 14.8, 15.2, 15.9 and 19.1 Gy for a single dose and doses in 1.5-, 1.0-, 0.8-, 0.6- and 0.4-Gy fractions, respectively. The data gave an alpha/beta of 2.1 Gy (95% CI, 1.4, 2.7 Gy). Pooling the data separately, the alpha/beta value was 2.3 Gy (95% CI, 0.82, 3.7 Gy) for fraction sizes > or = 1 Gy, and 1.2 Gy (95% CI, 0.16, 2.3 Gy) for the 0.8-, 0.6- and 0.4-Gy experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Secular changes in the outcomes to eighteen to twenty-four months of age of extremely low birth weight infants, with adjustment for changes in risk factors and severity of illness.

OBJECTIVES: To analyze secular changes in the rates of death and of major impaired outcome in surviving outborn infants who weighted < or = 800 gm at birth and were admitted in 1980 to 1989, with adjustment for changes in risk factors and severity of illness around the time of birth; and to identify changes in these factors that might explain changes in outcomes. DESIGN: Retrospective cohort study with follow-up to a minimum of 18 months of postterm age. After preliminary screening, multivariate models of association between risk/severity of illness factors and outcomes were constructed, validated, and used to adjust outcomes (death and major impairment to 18 to 24 months of age). SETTING: Regional neonatal intensive care unit for referral of "outborn" infants. PATIENTS: Two hundred eighty-seven consecutively admitted infants who weighted < or = 800 gm at birth (97% follow-up). RESULTS: The death rate during the 1980s did not fall significantly (p adjusted for risk factors = 0.115). The major impairment rate fell (odds ratio, 0.24 (95% confidence interval, 0.10, 0.60); p = 0.002, adjusted for delivery route and respiratory failure measures), mainly because of a reduced rate of blindness, not attributable to cryotherapy. The risk factors that improved and were possibly related to the reduced impairment rate were blood pH and glucose concentration, and serum sodium concentration in the first 48 hours of life. CONCLUSIONS: Despite an increasing selection for referral of less mature and more severely ill outborn babies near the "limit of viability," and despite more aggressive care, the rate of major impairment fell significantly during the 1980s. This trend was enhanced by adjustment for severity of illness. The fall was attributable to a reduced rate of blindness, and was associated with evidence of improved control of physiologic balance after birth.

Apgar Score↗

Envelopment of varicella-zoster virus: targeting of viral glycoproteins to the trans-Golgi network.

Previous studies suggested that varicella-zoster virus derives its final envelope from the trans-Golgi network (TGN) and that envelope glycoproteins (gps) are transported to the TGN independently of nucleocapsids. We tested the hypothesis that gpI is targeted to the TGN as a result of a signal sequence or patch encoded in its cytosolic domain. cDNAs encoding gpI wild type (wt) and a truncated mutant gpI(trc) lacking transmembrane and cytosolic domains were cloned by using the PCR. Cells transfected with cDNA encoding gpI(wt) or gpI(trc) synthesized and N glycosylated the proteins. gpI(wt) accumulated in the TGN, some reached the plasmalemma, but none was secreted. In contrast, gpI(trc) was retained and probably degraded in the endoplasmic reticulum; none was found on cell surfaces, but some was secreted. The distribution of gpI(trc) was not affected by deletion of potential glycosylation sites. To locate a potential gpI-targeting sequence, cells were transfected with cDNA encoding chimeric proteins in which the ectodomain of a plasmalemmal marker, the interleukin-2 receptor (tac), was fused to different domains of gpI. A chimeric protein in which tac was fused with the transmembrane and cytoplasmic domains of gpI was targeted to the TGN. In contrast, a chimeric protein in which tac was fused only with the gpI transmembrane domain passed through the TGN and concentrated in endosomes. We conclude that gpI is targeted to the TGN as a result of a targeting sequence or patch in its cytosolic domain.

Animals↗

[Histopathological and immunohistochemical study of ovarian polyembryoma].

A case of polyembryoma which is rare in ovarian malignant germ cell tumors was reported. Microscopically, numerous and variable embryoid bodies, surrounded by embryonic hepatoid tissues, trophoblastic cells and multiple elements, were observed. The results of immunohistochemical analysis were: (1) alpha fetoprotein (AFP) was not only shown positive in yolk sac cells among the embryoid bodies, in the endoderm and in the margins of the ectodermal cells, but also in multiple elements in the mucinous matrix. (2) Hepatoid tissues reacted positively to AFP and alpha antitrypsin (AAT) as well as to hCG. (3) By using hCG and human placental lactogen (hPL) as markers it is proven that among trophoblastic cells of the tumor, not only syncytiotrophoblastic cells but also the intermediate cells and the cytotrophoblastic cells could be identified.

Adult↗

[Rearrangements and fusion gene of AML1 and MTG8 in acute myeloid leukemia M2b].

The t(8;21) reciprocal chromosomal translocation is frequently associated with M2b type of acute myeloid leukemia (AML). Recently, two genes, MTG8 on chromosome 8 and AML1 on chromosome 21, were found. The t(8;21) translocation resulted in rearrangements of the two genes and formation of AML1/MTG8 fusion gene. To clarify the molecular characteristics of AML-M2b, we studied 41 patients with AML-M2b. By Southern blot and hybridization, the rearrangements of AML1 and MTG8 genes were detected in 24 of 30 and 22 of 28 patients, respectively. By means of reverse transcription and polymerase chain reaction (RT-PCR), the AML1/MTG8 chimeric transcript was found in all 37 patients. In 4 patients with AML-M2b of normal karyotype, AML1/MTG8 fusion mRNA and/or rearrangements of AML1 and MTG8 genes were detected. However, among 31 patients with other types of AML, these abnormalities were found in only one patient with AML-M6. These results suggest that rearrangements of AML1, MTG8 genes and/or AML1/MTG8 fusion gene could be regarded as gene marker of AML-M2b that can be applied in the diagnosis and monitoring of therapy and minimal residual disease.

Adolescent↗

[Study on the reversing effect of tripiperaquine on human multidrug resistant leukemic cell line K562/A02].

K562/A02 is a Cell line with multi-drug resistance established in our laboratory bey long term induction with adriamycin. In this paper, reversal of MDR in K562/A02 cell line by tripiperaquine is reported. The cytotoxicity and intracellular concentration of daunorubicin (DNR) in K562/A02 were measured by MTT colorimetric assay and spectrofluorimetry. The results showed that the sensitivity of K562/A02 to DNR was greatly enhanced by tripiperaquine at 10 micrograms/ml, with an 11-fold increase in cytotoxic activity. The intracellular concentration of DNR in K562/A02 was significantly increased after coincubation with 20 mumol/L tripiperaquine for 3 hours. Our results suggest that tripiperaquine might be used in clinical trial to reverse MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[The influence of macrophage on the rates of cultured rabbit lens epithelial cell proliferation and DNA synthesis].

Cell and H3-TDR liquid scintillation countings were adopted to investigate the influence of macrophage on the proliferative rate of cultured rabbit lens epithelial cells, in vitro. After 24 hours of the action of macrophage opsonic fluid on the cell culture, the rates of cell proliferation and DNA synthesis in the experimental group were higher than those of the control group (P < 0.05) and maintained so to the fifth day. It is demonstrated that the macrophage and its active factors can promote the proliferation of the lens epithelial cells, that is possibly related to the posterior capsular opacification after extracapsular cataract extraction.

Animals↗

[Lens epithelial proliferation induced by macrophages after intraocular lens implantation in rabbits].

To approach the effect of intraocular lens implantation on the mechanism of posterior capsular opacification, the pathological changes of posterior lens capsule after intraocular lens implantation in rabbits were observed by transmission electron microscopy. The results were as follows: In the control group, 1 week after the operation and the injection of the medium of the macrophage suspension, the lens posterior capsule was covered by a layer of lens epithelium and until post-operative 6 months, the lens epithelium remained normal. In the experimental group, 1 week after the operation and the injection of the macrophage suspension into the anterior chamber, microfilaments appeared in the cytoplasm of lens epithelial cells, after 2 weeks, the lens epithelial cells produced collagen fibrils in the extracellular matrix and until postoperative 3 months, 2-3 layers of the lens epithelium proliferated in front of the posterior capsule and a large amount of collagenous fibers were formed around the cells. It is suggested that the macrophage promote the lens epithelial proliferation and the posterior capsular opacification.

Animals↗

Outcome and prognosis in retroperitoneal soft tissue sarcoma.

PURPOSE: To retrospectively evaluate the outcome of treatment and identify factors prognostic for survival and locoregional and distant disease control for patients with retroperitoneal soft tissue sarcoma. METHODS AND MATERIALS: The records of 104 patients with retroperitoneal soft tissue sarcoma (RSTS) managed with surgery and irradiation at Princess Margaret Hospital between 1975 and 1988 were retrospectively reviewed. Univariate log-rank analysis was used to evaluate potential prognostic factors. RESULTS: Presentation was new primary disease, 74; primary recurrence, 20; metastases, 10. Pathology was liposarcoma for 42, leiomyosarcoma for 22, malignant fibrous histiocytoma for 19, and 21 with other histologies. Grade was low for 36, high for 35, and 33 were not graded. Median tumor size was 17 cm. Grossly complete surgical excision was achieved for 45 (43%), of whom 6 (6%) also had clear surgical margins. Adjuvant postoperative irradiation was administered to 36 patients to a median dose of 40 Gy/20 fractions/4 weeks and 16 received adjuvant chemotherapy. Nine patients received no adjuvant postoperative radiotherapy. Gross residual tumor was present postoperatively in 57 patients. The overall 5- and 10-year survival rates were 36% and 14%, respectively. The locoregional relapse free rate (RFR) was 28% at 5 years and 9% at 10 years, and the distant RFR was 76% at 5 years and 60% at 10 years. For the 45 patients treated with complete excision, survival was 55% and 22% at 5 and 10 years, and locoregional RFR was 50% and 18% at 5 and 10 years. Univariate analysis demonstrated that complete surgical removal was the only factor significant for improved survival, locoregional RFR, and distant RFR. Liposarcoma histology predicted for improved survival (p = 0.02), and leiomyosarcoma histology for a lower distant RFR, compared to other histologies (p = 0.003). Patients under 62 years had an improved survival (p = 0.002) and local RFR (p = 0.02), and patients presenting with recurrent disease had improved survival (p = 0.03). Sex, tumor size, or grade, or the use of adjuvant chemotherapy were not predictive for any of the endpoints tested. Those who received adjuvant irradiation following gross surgical clearance experienced a prolonged median locoregional RFR over those who did not, and this approached statistical significance for those receiving radiation doses > 35 Gy. (103 months vs. 30 months, p = 0.06). Statistical significance was reached (p = 0.02) if only the infield RFR was considered. CONCLUSIONS: This study demonstrates that failure to achieve local control is the primary cause of treatment failure for patients with RSTS, and that postoperative irradiation in doses > 35 Gy after complete surgery delayed, but did not prevent local recurrence. Improvements in outcome for patients with RSTS will require alternate treatment strategies, and preoperative irradiation with an aggressive surgical attempt at complete excision is currently under investigation.

Combined Modality Therapy↗

Quantitative effect of combined chemotherapy and fractionated radiotherapy on the incidence of radiation-induced lung damage: a prospective clinical study.

PURPOSE: The objective of this work was to assess the incidence of radiological changes compatible with radiation-induced lung damage as determined by computed tomography (CT), and subsequently calculate the dose effect factors (DEF) for specified chemotherapeutic regimens. METHODS AND MATERIALS: A prospective, clinical study was conducted to determine the response of normal lung tissue to combined chemotherapy and radiotherapy. Radiation treatments were administered once daily, 5 days-per-week. Six clinical protocols were evaluated: ABVD (adriamycin, bleomycin, vincristine, and DTIC) followed by 35 Gy in 20 fractions; MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) followed by 35 Gy in 20; MOPP/ABVD followed by 35 Gy in 20; CAV (cyclophosphamide, adriamycin, and vincristine) followed by 25 Gy in 10; and 5-FU (5-fluorouracil) concurrent with either 50-52 Gy in 20-21 or 30-36 Gy in 10-15 fractions. CT examinations were taken before and at predetermined intervals following radiotherapy. CT evidence for the development of radiation-induced damage was defined as an increase in lung density within the irradiated volume. The radiation dose to lung was calculated using a CT-based algorithm to account for tissue inhomogeneities. Different fractionation schedules were converted using two isoeffect models, the estimated single dose (ED) and the normalized total dose (NTD). RESULTS: A total of 102 patients were entered and 70 completed the study. Forty-two patients developed CT changes compatible with lung damage. The actuarial incidence of radiological pneumonitis was 71% for the ABVD, 49% for MOPP, 52% for MOPP/ABVD, 67% for CAV, 73% for 5-FU radical, and 58% for 5-FU palliative protocols. Depending on the isoeffect model selected and the method of analysis, the DEF was 1.11-1.14 for the ABVD, 0.96-0.97 for the MOPP, 0.96-1.02 for the MOPP/ABVD, 1.03-1.10 for the CAV, 0.74-0.79 for the 5-FU radical, and 0.94 for the 5-FU palliative protocols. CONCLUSION: Quantitative dose effect factors (DEF) were measured by comparing the incidences of CT-observed lung damage in patients receiving chemotherapy and radiotherapy to those receiving radiotherapy alone. The addition of ABVD or CAV appeared to reduce the tolerance of lung to radiation.

Antineoplastic Combined Chemotherapy Protocols↗

Equilibrium dialysis of metal-serum albumin. I. Successive stability constants of Zn(II)-serum albumin and the Zn(2+)-induced cross-linking self-association.

The binding of Zn(II) to human serum albumin (HSA) and bovine serum albumin (BSA) was intensively studied by equilibrium dialysis. The successive stability constants were obtained by least-squares fitting. For both the Zn(II)-HSA and Zn(II)-BSA systems, the successive stability constants are basically similar, though such constants for the latter generally slightly larger than those for the former; the order of magnitude of K1 and K2 was found to be approximately 10(5) M-1. The twelve binding sites found for Zn(II)-HSA and fourteen binding sites for Zn(II)-BSA can be divided into three and two different sets, respectively, but in both systems, there exist approximately three identical strongest binding sites. The binding equilibrium of Zn(II)-HSA markedly depends on the concentration of HSA. The type of Scatchard plots indicates the existence of the Zn(2+)-induced cross-linking self-association of HSA, which was found from Wyman plots to be the strongest at a concentration of Zn2+ in the range (4-6) x 10(-6) M. The maximum of the apparent self-association constants k2 so obtained was approximately 2.6 x 10(4) M-1. Such a self-association mechanism and the order of magnitude of K1 and K2 both to some extent support the inference that the zinc group ions are bound to the cysteinyl sulphur atoms.

Animals↗

Epigenetic lesions at the H19 locus in Wilms' tumour patients.

To test the potential role of H19 as a tumour suppressor gene we have examined its expression and DNA methylation in Wilms' tumours (WTs). In most WTs (18/25), H19 RNA was reduced at least 20-fold from fetal kidney levels. Of the expression-negative tumours ten retained 11p15.5 heterozygosity: in nine of these, H19 DNA was biallelically hypermethylated and in two cases hypermethylation locally restricted to H19 sequences was also present in the non-neoplastic kidney parenchyma. IGF2 mRNA was expressed in most but not all WTs and expression patterns were consistent with IGF2/H19 enhancer competition without obligate inverse coupling. These observations implicate genetic and epigenetic inactivation of H19 in Wilms' tumorigenesis.

Alleles↗

A procedure for estimating the dose modifying effect of chemotherapy on radiation response.

A procedure based on a logistic regression model was used to estimate the dose-modifying effect of chemotherapy on the response of normal tissues to radiation. The magnitude of this modifying effect is usually expressed as a dose-effect factor (DEF). Values > 1.0 indicate an enhancing effect of chemotherapy while values < 1.0 suggest a 'protective' effect. The DEF in the proposed procedure is expressed as a function of logistic regression coefficients, response levels and values of covariates in the model. The proposed procedure is advantageous as it allows consideration of both the response levels and the values of covariates in calculating the DEF. A plot of the DEF against the response or a covariate describes how the DEF varies with the response levels or a covariate describes how the DEF varies with the response levels or the covariate values. Confidence intervals of the DEF were obtained based on the normal approximation of the distribution of the estimated DEF and on a non-parametric Bootstrap method. An example is given to illustrate the proposed procedure.

Antineoplastic Agents↗

Outcome and prognostic factors in soft tissue sarcoma in the adult.

PURPOSE: To evaluate the outcome, patterns of failure and prognostic factors in this rare disease in adult patients treated at a single institution in the modern era. METHODS AND MATERIALS: The records of all patients (389 cases) with soft tissue sarcoma in the extremities, torso (excluding retroperitoneum), and head and neck managed between 1980 and 1988 were reviewed. A curative (radical) approach was used in 321 patients of whom 10% were recurrent lesions. The local management consisted of surgery alone in 54 cases, surgery and radiotherapy in 250 and radiotherapy alone in 17. Adjuvant chemotherapy was used as a policy for high grade lesions in the initial five years of the study (98 cases), but was omitted subsequently. RESULTS: Extremity lesions fared more favourably compared to head and neck and torso lesions (p = 0.02) with respect to survival. Extremity and torso lesions had significantly better local control (p < 0.0001) than in the head and neck where local failure was a common cause of death. A multiple Cox regression analysis revealed that resection margins, local extension of tumor, age at diagnosis, and grade correlated with local relapse and distant relapse was also associated with local extension, high grade and in addition, large lesions. Size appeared especially predictive for distant failure, the most common cause of death. Distant failure was not influenced by the use of adjuvant chemotherapy. Patients treated for recurrence in this series had significantly worse survival due to increased distant failure despite similar local control to primary cases. CONCLUSION: This series highlights the overall problem of distant failure in this disease. It also reaffirms the importance of obtaining local control both in the head and neck, where uncontrolled local disease is the major cause of death, and in general since local relapse appears to increase the risk of distant failure. It appears that the current staging systems should be reviewed in the light of the apparent effect of different prognostic factors.

Actuarial Analysis↗