Analysis of cytokine profiles in patients with human papillomavirus-associated neoplasms.
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Animals↗
Biomedical subjects
T C Wu
Publications and source records attributed to T C Wu.
Demonstration of human papillomavirus (HPV) genomic amplification and viral-like particles from CaSki cell line in SCID mice.
We demonstrate that from the CaSki cervical cancer cell line, integrated HPV-16 genome was amplified and viral-like particles were generated in an in vivo SCID mouse model. The in vivo tumor growth of several HPV-containing cell lines and 2 HPV-negative cell lines was examined in SCID mice. Tumor growth was noted with the HeLa, CaSki, ME-180, and MS751 cell lines within 2 months after subcutaneous injection. Squamous differentiation was appreciated in focal areas of tumors derived from CaSki and ME-180. In the CaSki tumors, DNA in situ hybridization revealed homogeneous staining of nuclei in some cells in the differentiated areas, suggesting HPV genomic amplification. In contrast, punctate or speckled patterns of hybridization were identified in the less differentiated areas, suggesting continued integration of the HPV genome. Immunocytochemical staining for HPV-16 L1 capsid protein showed it to be concentrated in cells from the differentiated areas, correlating with the results of hybridization. Electron microscopic studies revealed 50 nm uniform particles, consistent with HPV viral-like particles, in the nuclei of some cells in well-differentiated areas. Furthermore, Southern transfer and hybridization of the Hirt's extract from the CaSki tumors was positive for HPV-16 DNA, indicating non-integrated, low molecular weight HPV-16 DNA. Our results show HPV genomic amplification of integrated viral DNA and generation of HPV viral-like particles in CaSki cancer cells in SCID mice and that viral DNA amplification and the formation of viral-like particles are coupled to cellular differentiation. This experimental model provides a potential system for studying the molecular pathogenesis of HPV infections.
Animals↗
Coinfection of HPV-11 and HPV-16 in a case of laryngeal squamous papillomas with severe dysplasia.
Human papillomavirus (HPV) types 6 and 11 have been associated with benign laryngeal papilloma, while HPV-16 is occasionally associated with laryngeal carcinoma. In this study, a case of laryngeal squamous papillomas with severe dysplasia was evaluated for the presence of HPV infection. The biopsy specimens were taken from a 58-year-old female patient at two different time points 3 months apart. Architecturally, the tumor showed papillary configuration reminiscent of squamous papilloma. Cytologically, the lesion showed morphologic features characteristic of severe squamous epithelial dysplasia. HPV infection was determined by DNA in situ hybridization using type-specific HPV-DNA probes. HPV-11 probes demonstrated homogeneous nuclear staining, suggesting productive viral replication. In contrast, HPV-16 probe produced a speckled pattern, suggesting HPV-16 DNA integration. Normal laryngeal epithelium did not yield specific hybridization. The presence of HPV-11 and HPV-16 was confirmed by PCR using HPV type-specific primers. Immunocytochemical staining was performed to detect Ki-67, a proliferation marker, and p53. Ki-67 expression was demonstrated throughout the whole thickness of epithelium. Staining for p53 was negative. This study suggests that multiple HPV infections can occur in the same lesion and that HPV-16 infection and its DNA integration may contribute to the occurrence of severe dysplasia in the lesion described.
Cell Nucleus↗
Laryngeal survey in glyphosate intoxication: a pathophysiological investigation.
Respiratory aspiration is a serious potential complication of glyphosate-surfactant herbicide intoxication. From October 1, 1992 to June 30, 1996, we performed laryngeal evaluations in 53 cases to investigate the possible pathophysiological mechanism of glyphosate intoxication. There were 36 cases with significant laryngeal injury. The blood WBC count were significantly higher and the hospital stays were significantly longer in patients with laryngeal injury, when compared with patients with no laryngeal injury (Student t-test, P < 0.005). Laryngeal injury was strongly correlated with aspiration pneumonitis (mean 2 = 4.449, P < 0.05). We concluded that laryngeal injury may be the major cause of aspiration that leads to some degree of morbidity and mortality, following concentrated glyphosate-surfactant herbicide intoxication. Laryngeal survey may be indicated in cases of glyphosate-surfactant intoxication, to evaluate the severity of mucosal injury, and to apply adequate supportive management as early as possible to prevent from aspiration complications and even mortality.
Adult↗
Prevalence of human papillomavirus in middle ear carcinoma associated with chronic otitis media.
Squamous cell carcinoma of the middle ear (MESCC) is an uncommon tumor and is associated with a history of long-term chronic otitis media (COM) in most cases. Although the human papillomaviruses (HPVs) have been implicated in many human neoplasms, its role in the pathogenesis of MESCC has not been studied. Polymerase chain reaction (PCR) using consensus primers for the detection of HPV types 6, 11, 16, 18, 31, 33, 52b, and 58 was applied in screening fourteen cases of MESCC from archival material. Further subtyping was performed by restriction enzyme digestion of PCR products and by in situ hybridization method on tissue sections. Of the fourteen cases of MESCC, eleven were found to have HPV DNA. HPV-16 was detected in all positive cases. Five cases revealed both HPV-16 and -18. A history of long-term COM (> 3 years) was found in thirteen of the cases. This is the first report to localize HPV-16/18 in MESCC on both the tissue level and the molecular level. The high prevalence of HPV in COM-associated MESCC therefore provides a good model to explain the pathogenesis of chronic-inflammation-related human malignancies.
Adult↗
Fulminant hepatic failure as the first manifestation of Wilson disease: a report of two cases.
Two cases of fulminant hepatic failure as a first manifestation of Wilson disease are reported. They were diagnosed as acute hemolytic anemia initially, and took a fatal course despite intensive medical therapy. The main object of this report is to emphasize that Wilson disease must be included in the differential diagnosis of fulminant hepatic failure in children. Liver transplantation is the only effective means of treatment in patients presenting with fulminant hepatic failure, but this procedure is difficult to perform because of insufficient organ donation in Taiwan. The best treatment for Wilson disease is prevention through diagnosis at a presymptomatic stage, and institution of life-long therapy with D. penicillamine.
Adolescent↗
Histamine 2 receptor blocker-ranitidine and sinus node dysfunction.
BACKGROUND: Histamine 2 (H2) receptors were observed to be present in the sinus node. H2 receptor blockers could attenuate the histamine-induced increase in sinus rate and could thereby worsen sinus node dysfunction. However, the data pertaining to electrophysiological effects of H2 receptor blocker ranitidine on sinus node function are not available as yet, although bradycardia has been occasionally reported along with ranitidine. The present study evaluates the electrophysiological effects of ranitidine on sinus node function, and also determines the safety of administering ranitidine to patients suffering from sinus node dysfunction. METHODS: Thirty-nine patients with clinical diagnosis of sinus node dysfunction were selected for this study. Electrophysiological effects of intravenous injection of 150 mg ranitidine on sinus node function was evaluated. Tests were performed for 21 patients in the basal state (Group 1) and for 18 patients (Group 2) after autonomic blockade (propranolol 0.2 mg/kg, and atropine 0.04 mg/kg). The sinus cycle length (SCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), sinoatrial conduction time (SACT), atrio-His (AH) and His-ventricle (HV) intervals and blood pressure (BP) before and after ranitidine were analyzed. RESULTS: In Group 1, changes in SCL, SNRT, CSNRT, SACT, AH, HV and BP were not found to be significant. However, in Group 2, wherein the patients received ranitidine after autonomic blockade, it was observed that ranitidine significantly prolonged SCL (905.0 +/- 31.0 to 1000.0 +/- 40.0 msec, p = 0.001), decreased systolic BP (134.7 +/- 4.7 to 124.8 +/- 4.8 mmHg, p < 0.001), and diastolic BP (71.9 +/- 2.0 to 67.9 +/- 1.9 mmHg, p = 0.001), while the changes in SNRT, CSNRT, SACT, AH and HV were not significant. CONCLUSIONS: A clinical dose of 150 mg ranitidine must be administered by a slow intravenous infusion for at least 5 minutes in case of patients suffering from sinus node dysfunction. Continuous monitoring of BP and heart rate are necessary, especially in cases of autonomic denervation.
Adult↗
Inducible nitric oxide synthase expression in coronary arteries of transplanted human hearts with accelerated graft arteriosclerosis.
Inducible nitric oxide synthase (iNOS) is a high-output isoform of NOS that produces nitric oxide (NO), a nonspecific immune effector molecule. In some animal models of autoimmunity, the induction of iNOS has been shown to lead to inflammation and tissue damage, and it has been suggested that iNOS is an immune mediator in humans as well. Using in situ hybridization and immunohistochemical techniques, we demonstrate that iNOS mRNA and protein are present in the coronary arteries of transplanted human hearts with accelerated graft arteriosclerosis (AGA). iNOS is expressed in cells morphologically consistent with macrophages in the neointima of 7 of 10 of the transplanted vessels with AGA that were examined. In serial sections, these same cells express the macrophage marker CD68. In contrast, iNOS is absent from five native coronary arteries with atherosclerosis and absent from two normal coronary arteries. Although iNOS is expressed in macrophages in AGA, its role in the pathogenesis of AGA is unknown.
Adolescent↗
The painful experience of inappropriate therapy of snake bites: a report of two cases.
Recognizing the exact species of snake and specific antivenin administration are the most important modality of treatment for poisonous snake bites. In Taiwan, there are six kinds of medically important snakes--two species of Elapidae and four species of Viperidae. Two kinds of polyvalent antivenins and one monovalent antivenin are available. But for snake bites, questions about the prescription of antivenins are still the major problems addressed to the Poison Control Center. Improper use of antivenin may delay a patient's recovery from snake poisoning and even lead to mortality. Here, two cases of snake bites are presented. Each had severe complications and mortality as a result of inappropriate therapy, and the most rational management of snake bite in Taiwan is discussed, too.
Adult↗
Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen.
Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity. In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1). Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7. In the current study, we tested these recombinant vaccinia for in vivo protection against an E7+ tumor, TC-1, which was derived from primary epithelial cells of C57BL/6 mice cotransformed with HPV-16 E6 and E7 and c-Ha-ras oncogenes. All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection. Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden. These findings point out the therapeutic limitations of recombinant vaccinia expressing unmodified tumor antigens. Further, they demonstrate that modifications that reroute a cytosolic tumor antigen to the endosomal/lysosomal compartment can profoundly improve the in vivo therapeutic potency of recombinant vaccines.
Animals↗
Enteric pathogens associated with gastrointestinal dysfunction in children with HIV infection.
Infants and young children with HIV infection commonly suffer from gastrointestinal manifestations of their disease. Many HIV infected children have evidence of persistent diarrhoea, malabsorption, malnutrition or growth failure. The aetiology and pathogenesis of gastrointestinal dysfunction in HIV infected children have not been well defined. We performed immunocytochemical analyses on intestinal tissue from 19 HIV-infected children with gastrointestinal dysfunction or growth failure. None of these 19 children had microbial pathogens identified in faecal samples using standard microbiological methods. Intestinal tissues were obtained from the children by biopsy and were examined for antigens from Pneumocystis carinii, cytomegalovirus (CMV) and herpes simplex virus (HSV) using the avidin-biotin-complex immunohistochemical technique and monoclonal or monospecific antibodies. We detected at least one of these pathogens in samples from eight (42%) of 19 HIV infected children. P. carinii was the most prevalent pathogen, found in five of the eight HIV infected children. All of the children with intestinal pneumocystis infection were receiving prophylaxis directed at the prevention of pulmonary disease with this organism and none of them were undergoing active pulmonary infection. We also identified CMV antigens in intestinal tissues from four children and HSV antigens in intestinal tissues from one child. Two children were infected with more than one pathogen. On the other hand, none of these pathogens were found in the tissues obtained from 10 HIV-uninfected patients who had intestinal tissues obtained for chronic non-infectious diarrheal and inflammatory diseases (P < 0.01, Fisher's exact test). Our findings indicate that some children with HIV infection and gastrointestinal dysfunction may be infected with opportunistic pathogens despite negative analyses employing standard microbiological methods. Our study also indicates that HIV infected children can undergo intestinal infection with P. carinii despite the administration of standard immunoprophylactic regimens directed at the prevention of infection with this organism.
AIDS-Related Opportunistic Infections↗
Characterization of human papillomavirus type 57b: transforming activity and comparative sequence analysis as probes for biological determinants associated with high-risk oncogenic viruses.
The association of human papillomavirus type 57 (HPV-57) with premalignant and malignant tumors of the nasal cavity was previously reported (Wu et al., Lancet 341, 522, 1993). We determined the complete nucleotide sequence of HPV-57b (GenBank 37537), which was molecularly cloned from a benign fungiform papilloma, and compared it with other HPV types and HPV-57a, which was cloned from an inverted papilloma of the maxillary sinus by de Villiers et al. (Virology 171, 248. 1989). Comparative and phylogenetic analysis of amino acid sequences of the HPV-57b oncogenes E5, E6, and E7 were performed with HPV-6, 11, 16, and 18. Phylogenetic trees using the Jotun-Hein algorithm indicated a closer relationship of HPV-57b E5 and E7 with corresponding genes of HPV-18. Signature pattern analysis of these two oncogenes was also in agreement with a closer relatedness to HPV-16 and 18 oncogenes, which are associated with a high risk for malignant progression. Compared with 7861 bp of HPV-57a, HPV-57b had 7868 bp as well as differences in the restriction enzyme sites and the open reading frames, including at least five additional ones. To investigate the oncogenic potential of HPV-57b, NIH 3T3 and REF52 cells were cotransfected with two plasmids: pKP54. HPV-57b, which contains the HPV-57b genome, and pMT.neo.1, which confers resistance to G418. After selection in culture medium containing G418, 58% of the G418r NIH 3T3 colonies and 47% of the G418r REF52 colonies exhibited morphological transformation. These results indicate that the transcriptional regulatory elements and the oncoproteins of HPV-57b are active in vitro to induce cellular transformation, as are other high-risk HPV types.
3T3 Cells↗
Effect of age on intrauterine insemination with frozen donor sperm.
OBJECTIVE: To assess the effect of variables that influence the pregnancy outcome of intrauterine insemination with frozen donor sperm. METHODS: A retrospective analysis of 408 cycles of frozen donor sperm inseminations were studied. Cycle fecundity and cumulative probability of pregnancy were compared according to several variables. RESULTS: The pregnancy rate was 13.5% per treatment cycle and 57.3% per patient. By life-table analysis, the cumulative probability of pregnancy was 75.6% after 12 cycle attempts, but there was a plateau after seven cycles. The cycle fecundity after the seventh cycle was 0.05, compared with 0.16 during the first seven cycles. Age had a profound impact on cycle fecundity. The cycle fecundity for women age 35 or less, 35-40, and over 40 years old were 0.2, 0.12, and 0.06, respectively. The cumulative probability of pregnancy after seven cycles for women 35 years or younger was 88%, compared with 65 and 42% in women 35-40 and over 40 years old, respectively. The number of motile sperm inseminated for pregnant cycles was higher than that for nonpregnant cycles. The fecundity rates for cycles with five or fewer, five to ten, greater than ten to 20, and over 20 million motile sperm inseminated were 5, 11, 16, and 20%, respectively. CONCLUSION: The most significant predictors of the fertility of intrauterine insemination with frozen donor sperm were the women's age and the total number of motile sperm inseminated. Fecundity dropped after seven cycles of treatment.
Adult↗
The WAF1-mediated p53 growth-suppressor pathway is intact in the coronary arteries of heart transplant recipients.
It has been suggested that the interaction of cytomegalovirus (CMV) with the p53 tumor suppressor gene product plays a role in the development of coronary artery restenosis after angioplasty. CMV nucleic acids have been observed in the coronary arteries of allografted hearts, suggesting a possible role for the interaction of CMV with p53 in the development of accelerated graft arteriosclerosis in transplant recipients. Formalin-fixed, paraffin-embedded sections of coronary arteries from 19 transplanted hearts were immunostained for the p53 gene product using Target Unmasking Fluid (TUF)-mediated immunohistochemistry and the anti-p53 antibodies CM1 and DO7. Fresh-frozen sections of coronary arteries were also available from six of the 19 hearts, and these fresh-frozen sections were immunostained for the p53 gene product with the DO7 antibody and for WAF1 using the anti-WAF1 antibody EA10. Focal and weak staining for p53 was observed in smooth muscle and endothelial cells in two of 19 vessels, whereas the remaining 17 did not stain. CMV nucleic acids were previously shown in six of 13 of these hearts by in situ hybridization. The fresh-frozen sections of coronary arteries also did not stain for p53, but the smooth muscle cells in these vessels did stain intensely for WAF1. These results suggest three possibilities: (1) CMV-p53 interactions are not important in the development of accelerated graft arteriosclerosis; or (2) there is an interaction, but it is transient and not detectable at the time points examined in this study; or (3) there is an interaction, but binding of CMV to p53 leads to accelerated degradation of p53, as occurs with HPV-E6. The expression of WAF1 further suggests that the WAF1-mediated antiproliferative signal is intact in these vessels.
Coronary Artery Disease↗
Murine endodermal F9E cells, derived from the teratocarcinoma line F9, contain high basal levels of retinoic acid receptors (RARs and RXRs) but are not sensitive to the actions of retinoic acid.
Retinoic acid (RA)-induced endodermal differentiation of F9 teratocarcinoma cells is accompanied by altered of many genes, including the retinoic acid receptor (RAR) alpha, beta, and gamma and retinoic x receptor (RXR) alpha and gamma genes. In addition, RA enhances the binding of nuclear receptors to the RA responsive elements and increases the trans-activation of the RA-responsive genes in F9 cells. These data suggest that RA increases the overall function of RA receptors in F9 cells. However, the cell line F9E, established by long-term exposure of F9 cells to RA, is insensitive to RA. These cells expressed the genes for keratin 8 and tissue specific plasminogen activator (t-PA), which are characteristic of endoderm cells. Northern blot analysis showed that F9E cells expressed high basal levels of RAR and RXR mRNAs, but genes including the RARs and RXRs, which are normally regulated by RA in F9 cells, were no longer regulated in F9E cells. Further, F9E cells were not sensitive to the antiproliferative effect of RA. In these cells, high levels of RA receptors constitutively bound to RA responsive elements, but RA could neither increase the amount of RA receptor binding to the RA responsive elements, nor enhance the transcription of the RA target genes. These findings provide a possible explanation for insensitivity of endodermal cells to the actions of RA. Our data also indicate that the levels of endogenous RA receptors do not predict the degree of RA sensitivity, and that RA responsiveness might be a function of the cell's ability to regulate RA receptor genes.
Animals↗
Idiopathic dilatation of the pulmonary artery. A case presentation.
Idiopathic dilatation of the pulmonary artery is an uncommon, but not rare, congenital anomaly that is diagnosed by exclusion and generally has a benign clinical course. A left hilar mass on the chest x-ray film is the major presentation. The authors present a case of idiopathic dilatation of the pulmonary artery with posttraumatic chest pain clinically. After serial examinations, idiopathic dilatation of the pulmonary artery was diagnosed. They discuss the phenomenon of transpulmonary valvular pressure gradient and noninvasive tools for long-term follow-up, including transesophageal echocardiography and magnetic resonance imaging.
Diagnosis, Differential↗
Serum interleukin-6 levels reflect disease status of gastric cancer.
OBJECTIVES: Interleukin-6 (IL-6) has been shown to be associated with cancer development. However, its role in gastric cancer patients has never been investigated. Our intent was to investigate this role. METHODS: Using enzyme-linked immunosorbent assay, we determined the IL-6 levels in sera of patients with gastric cancer (n = 218), benign gastric lesions (n = 9), and hepatitis B (n = 9), and in normal subjects (n = 85). C-reactive protein (CRP) levels and Helicobacter pylori antibodies were simultaneously determined in 150 and 133 gastric cancer patients, respectively. Serial serum IL-6 levels were also measured in 14 gastric cancer patients. Six gastric cancer cell lines were examined for IL-6 secretion. For comparison, serum carcinoembryonic antigen levels in all gastric cancer patients were also determined. RESULTS: Mean IL-6 levels were significantly higher in patients with gastric cancer (10.0 +/- 9.5 pg/ml) than in patients with benign gastric lesions (2.6 +/- 0.5 pg/ml), in hepatitis B carriers (2.8 +/- 0.9 pg/ml), and in normal subjects (2.5 +/- 0.3 pg/ml). Gastric cancer patients with IL-6 > 10 pg/ml increased in a stage-related manner (p = 0.0001). Serum IL-6 levels increased when four patients had recurrence, whereas IL-6 levels decreased in 10 patients with a disease-free status after gastric resection. Serum IL-6 levels correlated moderately with serum CRP levels (r = 0.5, p < 0.01), but not with H. pylori antibody titers (p = 0.23). Serum IL-6 levels correlated with survival, but not as an independent prognostic indicator. Conversely, patients with CEA > 5 ng/ml increased in a stage-related manner, but this is not an effective reflection of disease progression. Five of six gastric cancer cell lines secrete IL-6. CONCLUSIONS: Serum IL-6 levels correlate with disease status of gastric cancer and may be used as a new tumor marker for monitoring treatment and response of gastric cancer patients.
Adenocarcinoma↗
Short-term effects of nasal pressure support ventilation in acute exacerbation of hypercapnic COPD.
BACKGROUND: If nasal pressure support ventilation (NPSV) can be used at the early stage of acute exacerbation of severe COPD, profound ventilatory failure may be prevented without the complication from delayed intubation. To our knowledge, no study has focused on this group of patients. METHODS: In this prospective study, BiPAP was used with three stages of settings each for 30 min as follows: pressure support (PS) 10 cmH2O without PEEP (stage 1), PS 10 & PEEP 5 cmH2O (stage 2), and PS 17 & PEEP 5 cmH2O (stage 3). Data of spontaneous breathing before and after NPSV each for 10 min were also recorded as baselines. RESULTS: One of our 10 male patients dropped out due to intolerance of the mask, who was intubated immediately. Data of the other nine patients showed that integrated diaphragmatic EMG, respiratory rate, end-tidal CO2, VT/Ti, and VE reduced significantly when compared between baselines and stage 3 values (p = 0.0121, 0.0026, 0.0005, 0.0116, 0.0111 respectively). VT and SaO2 increased significantly (p = 0.0265 & 0.0019). The above parameters showed no significant difference between stage 1 and 2. Maximum inspiratory and expiratory mouth pressure remained unchanged after NPSV. No obvious complication was noted. CONCLUSIONS: For patients with acute exacerbations of sever COPD, early and short-term use of NPSV at higher level of PS can significantly suppress inspiratory muscle activities and respiratory drive, and improve VE, respiratory rate, gas exchange and thoracoabdominal asynchrony. Respiratory muscle strength changes little. The addition of 5 cmH2O of PEEP to 10 cmH2O of PS has no obvious effect.
Acute Disease↗