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Biomedical subjects

Y Qi

Publications and source records attributed to Y Qi.

At least 19 recordsLinked to original sources

Hybrid antibody mediated veto of cytotoxic T lymphocyte responses.

Strategies are being sought that allow the induction of specific tolerance to allogeneic transplants without affecting other immune functions. The so-called veto effect has been described as one such technology where CD8+ cells suppress responses of class I MHC-restricted T-lymphocyte precursors to antigens expressed by those CD8+ veto cells. Yet, veto inhibition will not be able to provide complete tolerance to allogeneic grafts since it only operates on cell populations that express CD8. Other types of cells prevalent in most organs express different tissue-specific antigens that are recognized by alloreactive T-cells. Therefore, complete tolerance to an allogeneic transplant can only be achieved if all cellular components within the graft acquire the immune-inhibitory function. Here, we studied whether the veto effect could be exploited for this purpose nevertheless. We produced a hybrid antibody (HAb) combining a mAb specific for a class I MHC molecule with a soluble CD8 molecule. We found that this HAb specifically and effectively transferred veto inhibition to different stimulator cell populations. Thus, we have developed a strategy that promises to selectively and completely tolerize graft-specific CTLs without affecting normal immune responses.

Animals

Quantitation of the nucleophosmin/B23-translocation using imaging analysis.

We have previously detected by immunofluorescent assay that the cellular localization of nucleophosmin/B23 (NPM) shifts from the nucleolus to the nucleoplasm (NPM-translocation) after exposure of cells to multiple agents. In order to improve the quantification of the NPM-translocation, we have developed a digital imaging technique. Human Lo leukemia cells, MCF-7 breast carcinoma cells, and fresh human leukemia cells were exposed to anthracyclines or actinomycin D for 4 h. The degree of NPM-translocation was determined and presented as the localization index (LI). Control cells had a LI of about 10, which indicates that the majority of NPM was localized in nucleoli. The LI for drug-treated cells decreased in a dosage- and time-dependent manner. The effect of two classes of anthracycline (daunomycin and aclacinomycin A) and different types of intercalators (daunomycin and actinomycin D) had additive effects on induction of NPM-translocation. The imaging procedure was easily applied to fresh leukemia cells, thus providing useful information regarding drug effects on cancer cells.

Aclarubicin

Immunolocalization of hepatic metastases of human colonic cancer by chimeric anti-TAG72 antibody in SCID mice.

TAG72 is a well-characterized, human tumor-associated antigen present in > 85% of human colonic cancers. In this study, we established an animal model of hepatic metastases of human colonic carcinoma. The high-mucin variant cell line, designated HM7, was derived from the human colonic carcinoma cell line LS174T. Following intrasplenic injection, HM7 was able to induce much greater hepatic metastases in SCID mice compared to its parental cell line LS174T. Numerous hepatic metastases were evident 18 days subsequent to the intrasplenic injection of tumor cells. Using the chimeric anti-TAG72 antibody ccM4, immunohistochemistry demonstrated strong expressions of the TAG72 antigen in these metastases. Our biodistribution and imaging data also showed that the radiolabelled ccM4 antibody was able to localize hepatic metastases in the SCID mice. Based upon these findings, w anticipate that the herein described SCID mouse model will prove most useful in studying hepatic metastases of human colonic carcinoma by using anti-TAG72 therapeutic immunoreagents.

Adenocarcinoma

Antibody-targeted lymphokine-activated killer cells inhibit liver micrometastases in severe combined immunodeficient mice.

BACKGROUND & AIMS: Animal models for hepatic metastases can facilitate the investigation of lymphokine-activated killer (LAK) cell-based immunotherapy. The aim of this study was to investigate the efficacy of ccM4 antibody-targeted LAK cells in inhibiting hepatic micrometastases. METHODS: Hepatic micrometastases were generated after the intrasplenic injection of HM7 colon carcinoma cells. TAG72 expression was detected in these hepatic micrometastases using ccM4 antibody. The ccM4 antibody was conjugated onto LAK cells by treatment with 17.5% polyethylene glycol 8000. After the intrasplenic injection of HM7 cells, severe combined immunodeficient mice were randomized into five groups (i-v) and received either 10(7) ccM4-LAK cells plus 1000 U interleukin 2 (IL-2; group i), LAK cells plus 50 micrograms ccM4 and IL-2 (group ii), LAK cells plus IL-2 (group iii), IL-2 alone (group iv), or only phosphate-buffered saline (group v). RESULTS: The ccM4-LAK cells retained cytolytic activity and acquired TAG72-binding reactivity. The results showed that group i had significantly fewer hepatic metastases compared with group ii or group iii (P < 0.05) and even fewer hepatic metastases compared with group iv or group v (P < 0.001). CONCLUSIONS: These results show that ccM4 antibody-targeted LAK cells significantly inhibited tumor growth in vivo; thus, they can be potentially useful in treatment of hepatic micrometastases.

Animals

Characteristics of voicing source waveforms produced by esophageal and tracheoesophageal speakers.

Voicing source waveforms produced by 10 laryngectomized esophageal speakers, 12 laryngectomized tracheoesophageal speakers, and 10 age-matched, normal male speakers were obtained by inversely filtering flow functions recorded with a circumferentially vented mask. The data from these speakers was used to evaluate differences in source signal properties on a group basis. In a second analysis source signals produced by a single laryngectomized individual, capable of producing esophageal and tracheoesophageal speech in a highly proficient manner, were analyzed and compared. The overall results of this project provide an initial and novel description of voicing source signals produced by esophageal and tracheoesophageal speakers. The characteristics of these signals appear to be highly variable, particularly in comparison with the homogeneous pattern of source waves produced by age-matched, normal speakers. This initial description of voicing source signals produced by alaryngeal speakers is generally supportive of the hypothesis of differences in source properties among normal, esophageal, and tracheoesophageal voices.

Humans

Hypoxia alters iron homeostasis and induces ferritin synthesis in oligodendrocytes.

Both iron and the major iron-binding protein ferritin are enriched in oligodendrocytes compared with astrocytes and neurons, but their functional role remains to be determined. Progressive hypoxia dramatically induces the synthesis of ferritin in both neonatal rat oligodendrocytes and a human oligodendroglioma cell line. We now report that the release of iron from either transferrin or ferritin-bound iron, after a decrease in intracellular pH, also leads to the induction of ferritin synthesis. The hypoxic induction of ferritin synthesis can be blocked either with iron chelators (deferoxamine or phenanthroline) or by preventing intracellular acidification (which is required for the release of transferrin-bound iron) with weak base treatment (ammonium chloride and amantadine). Two sources of exogenous iron (hemin and ferric ammonium citrate) were able to stimulate ferritin synthesis in both oligodendrocytes and HOG in the absence of hypoxia. This was not additive to the hypoxic stimulation, suggesting a common mechanism. We also show that ferritin induction may require intracellular free radical formation because hypoxia-mediated ferritin synthesis can be further enhanced by cotreatment with hydrogen peroxide. This in turn was blocked by the addition of exogenous catalase to the culture medium. Our data suggest that disruption of intracellular free iron homeostasis is an early event in hypoxic oligodendrocytes and that ferritin may serve as an iron sequestrator and antioxidant to protect cells from subsequent iron-catalyzed lipid peroxidation injury.

Acids

Estimating parametric survival model parameters in gerontological aging studies: methodological problems and insights.

Studies of the biology of aging (both experimental and evolutionary) frequently involve the estimation of parameters arising in various multi-parameter survival models such as the Gompertz or Weibull distribution. Standard parameter estimation methodologies, such as maximum likelihood estimation (MLE) or nonlinear regression (NLR), require knowledge of the actual life spans or their explicit algebraic equivalents in order to provide reliable parameter estimates. Many fundamental biological discussions and conclusions are highly dependent upon accurate estimates of these survival parameters (this has historically been the case in the study of genetic and environmental effects on longevity and the evolutionary biology of aging). In this article, we examine some of the issues arising in the estimation of gerontologic survival model parameters. We not only address issues of accuracy when the original life-span data are unknown, we consider the accuracy of the estimates even when the exact life spans are known. We examine these issues as applied to known experimental data on diet restriction and we fit the frequently used, two-parameter Gompertzian survival distribution to these experimental data. Consequences of methodological misuse are demonstrated and subsequently related to the values of the final parameter estimates and their associated errors. These results generalize to other multiparametric distributions such as the Weibull, Makeham, and logistic survival distributions.

Aging

Minimizing the effect of period determination on the computation of amplitude perturbation in voice.

Current methods of computing amplitude perturbation present in human voices depend upon being able to accurately determine fundamental period. In this paper, two methods of estimating the amplitude perturbation present in human voices, which do not depend on accurate determination of the boundaries between fundamental periods, are described. In both of these methods, amplitude perturbation is computed as the variance of an ensemble of periods calculated after these periods have been aligned in time. In one method, time alignment is accomplished using zero-phase transformation. In the second method, an unconstrained dynamic programming procedure is used. The accuracy of estimating amplitude perturbation by these two methods is evaluated using synthetic and natural voice signals and is also compared with an estimation using zero-padding based time alignment. The unconstrained dynamic programming method is shown to provide accurate estimation of voice amplitude perturbation over a variety of signal conditions.

Female

Enhancement of female esophageal and tracheoesophageal speech.

Qi [J. Acoust. Soc. Am. 88, 1228-1235 (1990)] has demonstrated that (1) linear predictive (LP) methods can be used to separate vocal tract transfer functions from source functions of vowels produced by alaryngeal talkers and that (2) vowels synthesized with reconstructed transfer functions and totally synthetic voicing excitation sources have improved source-related properties over those present in the original vowels. Here, an extension of this work which is directed to the general goal of developing systems (devices) to enhance the quality of alaryngeal speech is reported. The specific goal of the present project was to determine whether speech, i.e., words spoken by female esophageal and tracheoesophageal talkers, could be enhanced by means of LP-based analysis and synthesis methods. Words spoken by four female alaryngeal talkers were analyzed and synthesized. A perceptual evaluation was completed to permit the quality of the synthetic and the original words to be compared. Listeners generally preferred to listen to the synthesized words, indicating that alaryngeal speech enhancement was accomplished.

Female

Isoform-specific retinoid-X receptor (RXR) antibodies detect differential expression of RXR proteins in the pituitary gland.

There are three known isoforms of the retinoid-X receptor (RXR): RXR alpha, RXR beta, and RXR gamma. RXR alpha and RXR beta messenger RNAs are widely expressed, whereas RXR gamma messenger RNA is restricted to only a few tissues, including embryonic pituitary gland. Little is known about the level of expression and cell distribution of RXR proteins in the adult pituitary gland. To examine these issues further, we raised isoform-specific polyclonal antibodies against each of the known mouse RXR isoforms using synthetic peptides containing isoform-specific epitopes from the amino-terminal region. The specificity of each antibody was confirmed by immunoprecipitation, Western immunoblot analysis, and electrophoretic mobility shift assay with supershift studies of in vitro translated RXR isoforms. Immunocytochemical analysis showed that anti-RXR alpha and anti-RXR beta antisera stained the nuclei of most pituitary cells. In contrast, anti-RXR gamma antiserum stained the nuclei of only a few cells throughout the pituitary. In the hypothyroid state, however, a marked increase in both the number and density of RXR gamma-immunostained nuclei were observed compared to those in the euthyroid state. Double immunostaining studies of hypothyroid rat pituitary with antibodies against pituitary hormones indicated that RXR gamma protein was predominantly expressed in thyrotropes. Antibody supershift experiments using nuclear extracts of adult rat whole pituitary and rodent pituitary cell lines showed that anti-RXR gamma antibody could alter the mobility of protein-DNA complexes formed only from nuclear extracts of rat whole pituitary and thyrotropic TtT-97 cells. In contrast, anti-RXR alpha and anti-RXR beta antibodies could supershift protein-DNA complexes formed from nuclear extracts of all cell lines tested. RXR gamma protein expression in TtT-97 cells also was observed by Western immunoblot analyses. Therefore, there is thyrotrope-predominant expression of RXR gamma protein. We speculate that RXR gamma may play a role in the regulation of thyroid hormone target genes in thyrotropes and possibly cell type differentiation in the pituitary.

Animals

Changes in adrenal status affect hypothalamic thyrotropin-releasing hormone gene expression in parallel with corticotropin-releasing hormone.

Glucocorticoids are well known to influence the secretion of TSH from the anterior pituitary gland, although it is uncertain whether its site of action is on the hypothalamus, pituitary, or both. To determine whether glucocorticoids can modulate the concentration of pro-TRH gene expression in hypothalamic hypophysiotropic neurons, we measured the content of pro-TRH messenger RNA (mRNA) in the paraventricular nucleus (PVN) of adrenalectomized and corticosterone- and dexamethasone-treated rats compared to that in control populations using in situ hybridization histochemistry. Adrenalectomy resulted in the expected increase in corticotropin-releasing hormone mRNA in the PVN and was accompanied by a parallel rise in pro-TRH mRNA (68.3%; P < 0.05). Conversely, corticosterone and dexamethasone both resulted in profound reduction in corticotropin-releasing hormone mRNA in the PVN and a parallel reduction in pro-TRH mRNA (43.2% and 73.2% respectively; P < 0.05). No significant differences were observed in pro-TRH mRNA in the lateral hypothalamus in any of the groups. These data suggest that glucocorticoids can influence the concentration of pro-TRH mRNA in a cell-specific manner and thereby could result in changes in the biosynthesis and release of TRH in hypophysiotropic neurons of the PVN.

Adrenal Glands

Fluoresein diacetate uptake to determine the viability of human fetal cerebral cortical cells.

We investigated the accuracy of fluorescein diacetate uptake as an indicator of the viability of human fetal cerebral cortical cells. Cortical cells from 16-26-week-old normal fetuses were studied. The cortices were dissociated mechanically with normal saline to make a suspension. Fluorescein diacetate uptake and trypan blue exclusion were compared as methods for examining cell viability. Our results show that fluorescein diacetate uptake is a simple and sensitive method for examining human fetal cortical cell viability.

Cell Survival

Laryngeal reconstruction and survival after function-sparing laryngectomy for selected T3 and T4 lesions.

Most patients lost their vocal ability after ablative surgery for the laryngeal cancer. Total laryngectomy has a history of over 100 years, hence many surgeons are accustomed to the en bloc organ resection and the loss of ability for communication after surgery. The recent advance of surgery introduces the concept and technique of radical cure and functional preservation of the cancer-afflicted-organ at the same setting. For lesions of late T categories (T3, T4), the maintenance of normal function after wide resection to ensure radicality demands a special technique to repair the crippled larynx. For this purpose a local osteomuscular flap was designed to reconstruct a functioning larynx. The surgical manoeuvre was described and the result proved to be successful. The outcome of 138 patients with T3 and T4 laryngeal carcinomas following conservation laryngectomy was analyzed. The five-year survival rate was 69% for supraglottic type and 75% for glottic type. The quality of life was much improved.

Adult

[A preliminary study of surgical therapy and combined therapy for cervical esophageal carcinoma].

52 patients with carcinoma of cervical esophagus were treated surgically. Their 3- and 5-year survival rate of was 38.5% and 35.1% respectively. The 3- and 5-year survival rate for surgery alone was 15.4% (2/13) and 9.1% (1/11). The 3- and 5-year survival rate for combined therapy (pre- or postoperative radiation and surgery) was 48.1% (13/27) and 52.9% (9/17). The 3- and 5-year survival rate for surgical salvage after failure of radical radiotherapy was 41.7% (5/12) and 33.3% (3/9). Our data suggest that the result of combined therapy is much better than the result of surgery or radiotherapy. The invation of recurrent nerve, hypopharynx, trachea, larynx and thyroid gland by tumor is contracindicated to surgery.

Adult

[The management of cervical esophageal cancer by head and neck surgeons].

Fifty-five cases of cervical esophageal cancer treated at the Department of Head and Neck Surgery, Cancer Hospital, are reported. The three and five year survival rates were 38.2% and 35%, respectively. There are advantages for head and neck surgeons over thoracic surgeons to deal with such cases. The low recurrence rate (7.3%) of this series was a result of high resection and anastomosis at the level of the hypopharynx and hence the better safety margin of tumor clearance. The lymph node metastasis of the neck and the involvement of other neck organs were no longer contraindications of surgery as observed by thoracic surgeons. However, the head and neck surgeons have difficulties in dissecting the mediastinal lymph nodes and in preparing the abdominal viscera while the stomach or colon is to be used to restore the continuity of the upper alimentary tract. Authors concluded that since the cervical esophageal cancer is a disease in the neck, it is reasonable to be managed mainly by head and neck surgeons and otolaryngologists under the support of thoracic and abdominal surgeons and radiotherapists.

Adult

Management of the orbital contents in radical surgery for squamous cell carcinoma of the maxillary sinus.

We reviewed retrospectively 139 patients with squamous cell carcinoma of the maxillary sinus who were treated with planned combinations of preoperative radiotherapy and maxillectomy between 1958 and 1987. The 5-year survival rate of these patients was 30%. In 111 patients who had tumor invasion of the orbital floor 88 underwent radical surgery with orbital exenteration and 23 had their orbital contents preserved. If orbital exenteration was performed, the 5-year survival rate was 27.3% (24/88) and the rate of recurrence within the orbit was 12.5%. In patients with preservation of the orbital contents, the corresponding rates were 34.8% (8/23) and 8.6% respectively (P = 0.65). Histological study after maxillectomy with orbital exenteration showed that in 95% of 65 specimens (62/65) invasion of the orbit was limited. These tumors could be completely resected by total maxillectomy with limited removal of the periorbital tissues after preoperative radiotherapy. We conclude that after preoperative radiation, the eyeball could be safely preserved in most selected patients with maxillary sinus carcinoma invading the orbital floor.

Adult

[High pressure liquid chromatographic determination of baicalin in lung-cleaning and diarrhoea-relieving infusion].

The baicalin in the compound recipe of traditional Chinese medicine Lung-cleaning and Diarrhoea-relieving Infusion was determined by reverse phase high pressure liquid chromatographic method. Methanol-water-tetrahydrofuran (200: 300: 50) was used as the mobile phase at ODS C-18 column with ultraviolet detection. The result showed that baicalin was separated well from other components. External standard method was used for quantitative determination. The recovery rate was 101.4% and RSD 0.83%.

Antidiarrheals