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Biomedical subjects

C Hu

Publications and source records attributed to C Hu.

197 records · Page 11Linked to original sources

Immunologic characterization of a granulocytic leukemia of inbred strain 13 guinea pigs: presence of Ia-positive myeloblasts.

Membrane markers expressed by a transplantable granulocytic leukemia induced in inbred strain 13 guinea pigs by N-nitroso-N-butylurea have been investigated by serologic and immunochemical methods. Although the leukemic myeloblasts have no detectable surface immunoglobulin or Fc receptors, they have been found to synthesize and express membrane antigens encoded for by the I-region of the major histocompatibility complex. Despite the presence of Ia antigens, these cells do not stimulate allogeneic T lymphocytes in the mixed lymphocyte reaction nor are they able to present soluble antigen to immune T cells. The presence of Ia antigens on immature myeloid cells suggests that these proteins may be important in cellular functions beyond those identified in the cellular immune system.

Animals↗

Serotherapy of avian reticuloendotheliosis virus-induced tumors.

Immune serum, obtained from animals that had survived sublethal challenge with RE virus, was very effective in achieving tumor cures in chickens infected with this virus. The therapeutic effect could also be obtained by the immunoglobulin fraction of immune serum. The serum did not influence the development of an unrelated malignancy. Serotherapy studies in Bx and Tx recipients indicate that the B-cell or T-cell system of the host does not significantly contribute to the curative activity of immune serum. Absorption studies show that the curative effect is mediated by antibodies to tumor-associated transplantation antigens on tumor cells, not by antiviral antibodies.

Animals↗

Solitary ulcers in reflux esophagitis: radiographic findings.

BACKGROUND: Some patients with reflux esophagitis have solitary ulcers in the distal esophagus. This study was undertaken to characterize further the radiographic features of these ulcers and to determine whether or not they have a predisposition to develop on the posterior esophageal wall. METHODS: Radiologic files and teaching files at our university hospital and affiliated Veterans Administration hospital revealed 29 patients with solitary reflux-induced ulcers. The radiographs were reviewed retrospectively to determine the size and location of the ulcers as well as the presence or absence of other findings. RESULTS: Twenty ulcers (69%) were located on the posterior wall, five (17%) on the left or right lateral wall, and four (14%) on the anterior wall. All but two ulcers were located 1-4 cm from the gastroesophageal junction. All of the ulcers were less than 10 mm in width and 5 mm in depth. Other associated findings included hiatal hernias in 11 patients (38%), mucosal nodularity or granularity in 12 (41%), one or more tiny satellite ulcers in three (10%), esophageal intramural pseudodiverticula in three (10%), an inflammatory esophagogastric polyp in one (3%), and scarring or stricture formation in 12 (41%). CONCLUSION: Our findings suggest that solitary reflux-induced ulcers tend to occur on the posterior wall of the distal esophagus near the gastroesophageal junction, producing characteristic radiographic findings. We postulate that affected individuals sleep primarily in the supine position, so that refluxed acid pools on the dependent or posterior esophageal wall, causing maximal injury in this location.

Adult↗

Expression of HOXD10 gene in normal endometrium and endometrial adenocarcinoma.

OBJECTIVE: Hox genes encode DNA transcription regulatory proteins that contain a conserved 61 amino acid protein called the homeodomain. Although best known for their role in cellular differentiation during embryonic development, aberrant expression of these genes has been associated with hematologic and solid neoplasms. The purpose of this study was to determine the relative expression of HOXD10 in human endometrial adenocarcinomas. METHODS: mRNA was isolated from 7 normal endometrial specimens and 28 endometrial adenocarcinoma specimens. cDNA was synthesized using random hexamer primers. The expression of HOXD10 relative to beta-tubulin (internal control) was assessed by densitometric comparison of co-amplified Phosphorus-32 (32P) labeled gene products separated by agarose gel electrophoresis. Direct sequencing of purified HOXD10 polymerase chain reaction product was also performed. RESULTS: The sequence of the purified HOXD10 product corresponds to the known DNA sequence reported in the National Institute of Health Gene Bank. mRNA expression of HOXD10 relative to beta-tubulin is significantly lower in endometrial carcinomas than in normal endometrium. Furthermore, the ratio of HOXD10 to beta-tubulin expression varies inversely with the histologic grade of the tumor (P = .0009). CONCLUSION: Cancer is a multistep process involving the aberrant expression of genes that regulate cell growth and differentiation. Human HOXD10 gene expression is altered in endometrial carcinoma and varies with the histologic grade of differentiation. This observation supports the theory that homeobox genes play a role in oncogenesis.

Adenocarcinoma↗

Expression of cyclin-dependent kinase inhibitors, p21cip1 and p27kip1, during wound healing in rats.

Wound healing is a physiological process in which growth of cells is stringently regulated. Cell growth is controlled by cell cycle-related proteins in which the cyclin kinase inhibitors cause cell cycle arrest and inhibit proliferation. However, little is known about the expression and the role of cyclin kinase inhibitors during wound healing in vivo. This study was mainly designed to examine the expression of p21cip1 and p27kip1 in excisional wounds of full-thickness skin in rats. Concomitant expression of proliferation marker Ki67 was also examined. Proliferation predominantly occurred in the first week after injury, peaking at postwounding day 5. Expression of both p21cip1 and p27kip1 at the gene and protein levels did occur during wound healing and showed an inverse gradient to that of Ki67. Constitutive p27kip1 was expressed throughout wound healing with low levels during the proliferating period of days 3 and 5 and increased levels during post-mitotic and remodeling stages. In contrast, p21cip1 was expressed transiently with detectable levels only between days 7 and 14 by Western blot analysis. Immunohistochemically, epithelial cells, endothelial cells and fibroblasts all could express both p21cip1 and p27kip1. In conclusion, the overall results suggested that p21cip1 and p27kip1 may play a key role in supervising the growth resulting from cell proliferation in tissue repair.

Animals↗

Incorporating the time dimension in receiver operating characteristic curves: a case study of prostate cancer.

Early diagnosis of disease has potential to reduce morbidity and mortality. Biomarkers may be useful for detecting disease at early stages before it becomes clinically apparent. Prostate-specific antigen (PSA) is one such marker for prostate cancer. This article is concerned with modeling receiver operating characteristic (ROC) curves associated with biomarkers at various times prior to the time at which the disease is detected clinically, by two methods. The first models the biomarkers statistically using mixed-effects regression models, and uses parameter estimates from these models to estimate the time-specific ROC curves. The second directly models the ROC curves as a function of time prior to diagnosis and may be implemented using software packages with binary regression or generalized linear model routines. The approaches are applied to data from 71 prostate cancer cases and 71 controls who participated in a lung cancer prevention trial. Two biomarkers for prostate cancer were considered: total serum PSA and the ratio of free to total PSA. Not surprisingly, both markers performed better as the interval between PSA measurement and clinical diagnosis decreased. Although the two markers performed similarly eight years prior to diagnosis, it appears that total PSA performed better than the ratio measure at times closer to diagnosis. The area under the ROC curve was consistently greater for total PSA than for the ratio four and two years prior to diagnosis and at the time of diagnosis.

Adult↗

Characterization and evaluation of a novel exalting round-plate photocatalytic reactor.

A novel reactor, the exalting round-plate photocatalytic reactor (ERPPR), was designed and evaluated. Residence time and light intensity distributions were determined by stimulus-response experimentation and an irradiation meter, respectively. The effects of hydraulic loading of the round plate and aeration on the photocatalytic degradation of azo dye were investigated during different conditions. Experimental results show that the ERPPR is intermediate between a completely stirred tank reactor and a plug-flow reactor. Mean hydraulic loadings at different rotational speeds were significantly influenced by the reaction rate for dye decolorization. Photodegradation of the dye, however, was not significantly influenced by the amount of oxygen gas aerated, except when aerating with pure oxygen. Results further indicate that the photoreaction atmosphere of the ERPPR depends on mass transfer between gas and liquid on the round plate. The primary role of aeration is to mix catalyst and solution.

Catalysis↗

Inflammatory intermediates produced by tissues encasing silicone breast prostheses.

Silicone prostheses, when implanted within the soft tissues of the breast, evoke an inflammatory reaction. In response to silicone exposure, inflammatory mediator production by individual cells has been observed in various experimental studies. In this study, inflammatory mediator production by periprosthetic tissues (whole organ) was measured. The mediator levels were correlated with both the tissue histopathology of the periprosthetic capsules and the clinical symptoms noted by each patient. Tissue surrounding breast implants removed at surgery from ten women (average age and implant duration 40 and 7 years respectively) was cultured in vitro for 24 hours. Control tissues consisting of (a) augmentation mammaplasty skin scars from eight additional patients and (b) knee synovium from seven orthopedic surgery patients with arthritis undergoing primary joint arthroplasty were similarly cultured. The mediators [interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and prostaglandin E2 (PGE2)] liberated into the culture media were measured by an enzyme linked immunosorbent assay. When compared to controls, the mediator levels of IL-6 and TNF-alpha were substantially greater, although IL-2 and PGE2 were lower. Levels varied greatly from patient to patient: in pg/ml per 10 g tissue, IL-2 ranged from 10 to over 1,000; TNF-alpha from 100 to 1,000; IL-6 from 100 to 1,000,000; and PGE2 from 100 to 10,000. The correlation between TNF-alpha and PGE2 levels was .5 between IL-6 and PGE2 was .6, and between IL-6 and TNF-alpha was .77. The correlation between TNF-alpha and IL-6 was statistically significant at a p-value less than .01. Elevated levels of TNF-alpha production were associated with an increased number of macrophages and overall tissue cellularity (p < .05). No significant relationship was observed between mediator production and clinical symptoms. We conclude that overall cellularity, specifically macrophages, in the periprosthetic capsule may lead to TNF-alpha production but that cytokine production by periprosthetic tissues alone is not a predictor of clinical symptomatology in patients with silicone breast prostheses.

Adult↗

What are the implications of cardiac infection with cytomegalovirus before heart transplantation?

To elucidate prognostic implications of recipient cytomegalovirus infection before heart transplantation, we prospectively followed the clinical outcome of 21 transplant recipients whose explanted hearts (myocardium and coronary arteries) were first examined for the presence of cytomegalovirus DNA with polymerase chain reaction. Subsequently, serial endomyocardial biopsy tissue samples obtained from the allograft during routine evaluation for rejection were analyzed by polymerase chain reaction for both an immediate early and late cytomegalovirus gene region of cytomegalovirus DNA. Humoral cytomegalovirus immunoglobulin G antibodies were also measured by radioimmunoassay. Both early and late antigens were present in 14 of 21 (67%) explants from patients with (12 of 15 explants) and without (2 of 6 explants) pretransplant cytomegalovirus antibodies. Although the presence of both early and late antigens was uncommon in allografts the first week after transplantation (5 of 20 allografts, 25%), their presence significantly increased at 1 month (14 of 21 allografts, 67%) and 2 to 3 months (13 of 17 allografts, 77%) regardless of pretransplantation cytomegalovirus antibody status. The presence of both early and late antigens in explant tissue strongly predicted allograft virus status during the follow-up periods. Of five patients in whom clinical cytomegalovirus disease subsequently developed, all had explants positive for both early and late antigens, and all allografts were positive for early and late antigens within 1 month after transplantation. These are the first prospective data to correlate pretransplantation serum antibodies and explant polymerase chain reaction status with the development of future allograft infections and overall clinical outcome.

Adult↗

Gene therapy with an adeno-associated virus carrying an interferon gene results in tumor growth suppression and regression.

Adeno-associated virus (AAV) vectors were constructed containing both a synthetic type I interferon gene, (IFN-con1) and the bacterial neomycin-resistant gene. Recombinant virions were used to infect a number of human tumor cell lines, including 293, Hela, K562, and Eskol (a hairy cell leukemia-like cell), and geneticin-resistant cells were selected. All IFN-con1-transduced cell lines produced low levels of IFN-con1 and grew at the same rate as nontransduced cell lines. Although these cell lines were resistant to IFN in vitro, when injected into nude mice, 293, K562, and Eskol cells failed to form tumors up to 3 months after the initial inoculum, although mice receiving nontransduced cells developed tumors within 7 to 10 days. Transduced Hela cells grew much slower in vivo and formed much smaller tumors than did the parental cells. When equal numbers of transduced and nontransduced cells were injected into nude mice, tumors initially developed slowly and then completely regressed. Treatment of an established Eskol tumor (histologically a malignant immunoblastic lymphoma) with AAV/IFN-con1-transduced 293 cells resulted in tumor regression, whereas treatment of Eskol tumors with IFN-con1 resulted in a small decrease in tumor size. These results indicate that the human IFN-con1 gene in a viral vector can be used successfully in the treatment of tumors both directly and by tumor-targeted gene therapy.

Animals↗

p16 overexpression: a potential early indicator of transformation in ovarian carcinoma.

OBJECTIVE: The recently cloned gene p16 (MST1) has been identified as a putative tumor suppressor gene that binds to CDK4 and CDK6 (cyclin-dependent kinases), preventing their interaction with cyclin D1 and thereby preventing cell cycle progression at the G1 stage. In addition, the p16 gene has been shown to have a high frequency of mutation in some tumor cell lines; however, it has also been shown that a much lower frequency of mutation occurs in primary tumors. This study investigated the mRNA expression level and mutation status of the p16 gene in ovarian tumors. METHODS: We performed quantitative polymerase chain reaction and direct cDNA sequencing analysis. To confirm the p16 protein level in ovarian tumors, Western blotting and immunohistochemical staining were performed. Expression levels of mRNA for the p16 gene relative to the beta-tubulin gene were examined in 32 ovarian tumors (24 carcinomas, six low malignant potential tumors, and two benign tumors) and six normal ovaries. RESULTS: The mRNA expression level of p16 was significantly elevated in 28 ovarian tumors (22 carcinomas, five low malignant potential tumors, and one benign tumor) compared with that of normal ovaries. Western blotting analysis and immunohistochemical staining confirmed elevated p16 protein levels in ovarian tumor samples. Among 32 ovarian tumors, cDNA sequencing of the p16 gene showed no p16 mutation resulting in a coding error, although one silent mutation and three polymorphisms were found. CONCLUSIONS: Although p16 is seldom mutated in ovarian tumors, the overexpression of p16 in most ovarian tumor cases indicates a dysfunction in the regulatory complex for G1 arrest. Therefore, overexpression of p16 may be an important early event in the neoplastic transformation of the ovarian epithelium.

Biomarkers, Tumor↗