Workgroup 2: human xenograft models of prostate cancer.
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Publications and source records attributed to C J Chang.
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We prospectively studied the gender differences of baseline variables, therapies, and outcomes among a cohort of 369 Chinese patients with acute myocardial infarction from 1990 to 1995. There were 277 male and 92 female patients. The male gender had a younger mean (+/-SD) age (61.5+/-10.7 vs. 67.1+/-11.7 years, P<0.0001). Hypercholesterolemia (201.2+/-44.2 vs. 187.5+/-43.7 mg/dl, P=0.0111) and obesity (25.0 vs. 15.9%, P=0.0494) were more prominent in the female. Smoking was more prevalent in the male (78.3 vs. 18.5%, P<0.0001). The male group also had more frequent use of thrombolytic agents (19.1 vs. 9.8%, P=0.0377), beta-blockers (61.7 vs. 47.8%, P=0.0191) and heparin (25.3 vs. 12.0%, P=0.0075); but less use of angiotensin-converting enzyme inhibitors (6.9 vs. 15.2%, P=0.0149). The condition on admission was worse in the female group (Killip classification (1.5+/-0.9 vs. 1.9+/-1.0, P=0.0022), myocardial failure (8.7 vs. 2.9%, P=0.0178) and cardiomegaly (65.2 vs. 53.1%, P=0.0419). During a follow-up duration of 26.4+/-24.1 and 22.9+/-23.9 months respectively, the mortality rate was lower in the male (19.5 vs. 30.4%, P=0.0288). However after adjustment for the effect of age, the differences in Killip classification, myocardial failure, cardiomegaly and mortality became insignificant.
Transcription factor C/EBPbeta has been known to regulate a wide array of genes including those involved in the acute-phase response. One of the molecular mechanisms underlying transcription activation by C/EBPbeta is through protein-protein interaction with other transcription factors. Here we report the identification and characterization of physical and functional interactions between C/EBPbeta and heterogeneous nuclear ribonucleoprotein (hnRNP) K. This interaction results in the repression of C/EBPbeta-dependent trans-activation of the agp gene. Footprinting assays indicate that hnRNP K cannot bind to the promoter region of agp gene or interfere with the binding of C/EBPbeta to its cognate DNA site. Furthermore, agp gene activation by the synergistic interaction of Nopp140 and C/EBPbeta is abolished by hnRNP K. The kinetics of appearance of C/EBPbeta-hnRNP K complex in the nuclear extract after initiation of acute-phase reaction indicates that hnRNP K functions as a negative regulator of C/EBPbeta-mediated activation of agp gene.
BACKGROUND: Genital human papillomavirus (HPV) infection is highly prevalent in sexually active young women. However, precise risk factors for HPV infection and its incidence and duration are not well known. METHODS: We followed 608 college women at six-month intervals for three years. At each visit, we collected information about lifestyle and sexual behavior and obtained cervicovaginal-lavage samples for the detection of HPV DNA by polymerase chain reaction and Southern blot hybridization. Pap smears were obtained annually. RESULTS: The cumulative 36-month incidence of HPV infection was 43 percent (95 percent confidence interval, 36 to 49 percent). An increased risk of HPV infection was significantly associated with younger age, Hispanic ethnicity, black race, an increased number of vaginal-sex partners, high frequencies of vaginal sex and alcohol consumption, anal sex, and certain characteristics of partners (regular partners having an increased number of lifetime partners and not being in school). The median duration of new infections was 8 months (95 percent confidence interval, 7 to 10 months). The persistence of HPV for > or =6 months was related to older age, types of HPV associated with cervical cancer, and infection with multiple types of HPV but not with smoking. The risk of an abnormal Pap smear increased with persistent HPV infection, particularly with high-risk types (relative risk, 37.2; 95 percent confidence interval, 14.6 to 94.8). CONCLUSIONS: The incidence of HPV infection in sexually active young college women is high. The short duration of most HPV infections in these women suggests that the associated cervical dysplasia should be managed conservatively.
BACKGROUND AND OBJECTIVES: En bloc esophagectomy has been established as the treatment of choice for patients with resectable esophageal carcinoma. However, an extensive surgical procedure may result in further impairment of the patient's nutritional status and immune system. Thus a prospective study was undertaken to evaluate the perioperative sequential changes in patients' nutritional and immune status and the timing to institute postoperative adjuvant therapy. METHODS: Thirty-seven patients (34 male, 3 female) who had undergone en bloc esophagectomy with gastric institution for epidermoid carcinoma of the esophagus were studied. The mean age was 62.3 years. The nutritional and immune assessments were performed preoperatively, on the third postoperative day, in the first week, second week, third week, and at the end of the first and third month. The biochemical studies for nutritional evaluation included serum albumin, cholesterol, iron, transferrin, magnesium, zinc, total iron binding capacity (TIBC), and nitrogen balance. Evaluation of the immune status consisted of: (1) total lymphocyte count, (2) lymphocyte subpopulation, (3) immunoglobulins, (4) complements (C3 and C4), (5) lymphocyte blastogenic responses, (6) tumor necrosis factor-alpha and interleukin-2 secretion activity from mononuclear cells, and (7) C-reactive protein (CRP) level. RESULTS: All the parameters in nutritional assessment declined profoundly by the third postoperative day (P < 0.05). The most severe deterioration was in serum iron, followed by transferrin, TIBC, cholesterol, and zinc. Most of them returned to the preoperative levels within 2-3 weeks after surgery. However, the serum levels of iron, transferrin, and TIBC required a longer period of time (> 1 month) to return to normal. A remarkable increase of serum CRP was detected in the first postoperative week (P < 0.05), but immunoglobulins and complements decreased significantly yet variably (P < 0.05) in the second or third postoperative week before gradually returning to preoperative levels. Moreover, during the first week after surgery, CD3 and CD8 diminished following esophageal surgery, whereas CD20, CD4/CD8 ratio, and lymphocyte blastogenic responses increased significantly (P < 0.05). CONCLUSIONS: Except for iron-related parameters, all the other nutritional parameters returned to the preoperative level by the third postoperative week. An adequate supplementation of iron and protein for 1-3 months after surgery is needed. En bloc esophagectomy might have only a mild and temporarily adverse effect on the host immune defense. Regarding the postoperative recovery of a patient's nutritional and immune status, postoperative chemo-radiotherapy is optimally instituted after the third postoperative week, instead of within 2 weeks of surgery.
Diabetes mellitus is one of the major health care problems in Taiwan, since the mortality rate has increased from 7.91 per 100,000 in 1980 to 35.1 per 100,000 in 1996. To determine the prevalence of diabetes in southern Taiwan and to investigate possible associated factors, a stratified systematic cluster sampling of 1638 subjects (780 men and 858 women) aged > or =20 years living in Tainan city was investigated with a standard 75-g oral glucose tolerance test. The crude prevalence of diabetes in Tainan was 9.0% (10.3% men and 7.9% women) and the age-adjusted prevalence was 9.2% (10.4% men and 8.1% women). The crude prevalence of IGT was 14.0% (13.8% men and 14.1% women), and the age-adjusted prevalence was 15.5% (15.0% men and 15.9% women). The prevalence of diabetes by using the revised new diagnostic criteria was 7.5%. The prevalence of diabetes and IGT increased significantly with age for both genders, although the rises in prevalence of IGT in women was less consistent. Diabetic and IGT subjects were older and had higher levels of BMI, triglyceride, systolic and diastolic blood pressure, and higher prevalence of obesity, hypertension, and dyslipidemia but indulged in less physical activity than non-diabetic subjects. The significant factors associated with the newly diagnosed diabetes were age, family history of DM, BMI, systolic blood pressure, physical activity, and serum triglyceride levels.
Obesity-related metabolic disorders have not been adequately addressed due to a failure to distinguish the importance of general obesity or body fat distribution in relation to atherosclerotic risk factors, especially in the less obese populations. To assess the relationship between general obesity (reflected by BMI, total body fat percentage and total adiposity), body fat distribution (reflected by WHR, default regions and ROIs of DEXA) and atherosclerotic risk factors in the Chinese population, a total of 872 healthy subjects (477 male and 395 female) were enrolled in the study. The results indicated that the android pattern of fat distribution, independent of general obesity, was positively correlated with blood pressure, atherogenic indices, fasting and OGTT 2-h plasma glucose, glycosylated hemoglobin (HbA1c), serum concentration of cholesterol, triglyceride, LDL cholesterol and negatively correlated with HDL cholesterol in both genders. The gender differences in patterns of body fat distribution and atherosclerotic risk factors remained significant after adjustments were made for age, BMI and total adiposity, although diminished after further adjustments for body fat distribution. In conclusion, body fat distribution, rather than general obesity, is more correlated with obesity-related atherosclerotic risk factors and sex-associated differences. ROIs measured by DEXA may be a useful method to evaluate sex-associated changes in body fat distribution and atherosclerotic risk factors in the healthy Chinese population.
Paraoxonase (PON1) is a high density lipoprotein-associated enzyme capable of hydrolyzing lipid peroxides, and thus, might protect lipoproteins from oxidation. A common polymorphism due to an amino acid substitution (Gln-Arg) at codon 191 is considered to be a major determinant of variation in serum PON1 activity. Recent studies have suggested that the PON1-191 polymorphism is an independent risk factor for coronary atherosclerosis in patients with or without diabetes mellitus. The association of PON1-191 polymorphism genotypes and coronary artery disease (CAD) among Chinese subjects in Taiwan was examined. The genotype of 218 angiographically documented CAD patients and the same number of age- and sex-matched control subjects was determined. Genotypes AA, AB and BB were present in 25 (11%), 102 (47%) and 91 (42%) of control subjects, respectively, and in 30 (14%), 96 (44%) and 92 (42%) of CAD patients, respectively (chi2 = 0.57, P = 0.75 between groups). The frequency of the A allele was 0.36 for the control group and 0.35 for CAD patients (P = 0.94). No significant differences in the PON1-191 genotype frequencies could be found between groups when multivariate logistic regression analysis was performed, or different subgroups of age, sex or risk factors were analyzed. Among control subjects, there was also no significant difference between genotypes of the PON1-191 polymorphism and various clinical and lipid variables. In conclusion, our data suggest that there is no association between the Gln-Arg 191 polymorphism of the human PON1 gene and CAD among Chinese subjects in Taiwan.
BACKGROUND: Advanced HIV infection is associated with increased serum IgE levels, which in turn have been associated with a poor prognosis. Our preliminary data revealed that serum IgE levels were significantly elevated in HIV seropositive injection drug users compared with HIV seropositive non-injection drug users. Since viral hepatitis is common among injection drug users and is itself associated with elevated serum IgE levels, we studied whether there was an association between increased serum IgE levels and positive hepatitis serology in HIV-seropositive patients. METHODS: A retrospective cross-sectional analysis was performed. The medical records of ambulatory HIV-infected patients in an ongoing study were reviewed. Forty-five patients had hepatitis A, B, and C serology performed. The associations between serum IgE levels and hepatitis A, B and C antibodies, CD4 and CD8 lymphocyte percentages, injection drug use, and sex were analyzed by univariate and multiple regression analyses. RESULTS: On univariate analyses, hepatitis B antibody was significantly associated with increased serum IgE levels in HIV-infected subjects (P = .013), especially in those with AIDS (P = .015). Multiple regression analyses controlling for CD4 lymphocyte percentages, sex, and drug use, confirmed that hepatitis B antibody status remained significantly associated with increased serum IgE levels (P = .05). There was no association of serum IgE levels with hepatitis A or C serology. CONCLUSION: Prior hepatitis B infection is significantly associated with increased serum IgE levels in advanced HIV infection. The clinical implications of this finding deserve further study.
BACKGROUND: Increased serum IgE levels are associated with advanced HIV infection. The magnitude of the increase has varied greatly between studies which generally did not assess potential confounding factors. OBJECTIVE: To determine whether the increased serum IgE levels reported with HIV infection is affected by demographic or behavioral factors, we studied injection drug users, women, and minority ethnic and racial groups with HIV infection, for whom little data now exist. METHODS: A prospective cross-sectional study of ambulatory patients with or at risk for HIV infection was performed. We enrolled 83 injection drug users and 56 non-drug users seropositive for HIV and 43 seronegative at-risk individuals from an Infectious Diseases clinic and a longitudinal study of HIV infection in injection drug users in the Bronx, New York City. Fifteen HIV-seronegative non-atopic controls were also studied. Total serum IgE levels were measured by a solid phase fluorescent assay and lymphocyte phenotypes were measured by monoclonal antibodies. RESULTS: On multiple linear regression analysis, HIV infection (P=.01) and advanced HIV disease (P < or =.01) were independently associated with increased serum IgE levels, controlling for gender, race, age, and use of injection drugs. In both HIV-seronegative and seropositive individuals, female gender was independently associated with lower IgE levels (P < or = .001). We did not find an independent effect of race or injection drug use on IgE levels. CONCLUSIONS: Increased serum IgE levels were associated with HIV infection, the highest levels existing in those with advanced HIV disease. Women had lower IgE levels than men, independent of HIV status. Active or past drug use, race, and age were not found to be independently associated with serum IgE levels. Further studies are necessary to elucidate the mechanisms underlying the increased serum IgE levels seen with HIV infection and its associated immunodeficiency, and to substantiate and explore the decreased levels found in women.
The effects of oral supplementation of a 30-mg dose of beta-carotene on the plasma levels of carotenoids, tocopherols, and retinol were studied sequentially in 69 patients participating in a nine-month randomized placebo controlled trial conducted to examine efficacy of beta-carotene to induce regression of cervical intraepithelial neoplasia. At each visit (baseline and 1.5, 3, 6, 9, 10.5, and 15 mo), blood samples were collected and the levels of six micronutrients were determined by high-performance liquid chromatography. No limitations or changes were introduced in each participant's dietary habits. Cervico-vaginal lavage samples were also obtained at the same visit and assayed for the presence of human papillomavirus DNA by Southern blot hybridization and polymerase chain reaction. In the supplemented group, mean plasma beta-carotene levels were significantly higher (p = 0.0001) than baseline and remained markedly elevated for 15 months. In the longitudinal analysis of the placebo group, there were no variations among individual mean plasma levels of beta-carotene, alpha-carotene, lycopene, retinol, gamma-tocopherol, or alpha-tocopherol, suggesting absence of seasonal or dietary changes. In the placebo group, cigarette smoking and steroid contraceptive use were significantly associated with low levels of plasma beta-carotene (p = 0.05 and p = 0.012, respectively). However, in contrast, in the beta-carotene-supplemented group, steroid contraceptive use had no influence on the plasma beta-carotene levels. An additional noteworthy finding was that beta-carotene supplementation did not reverse the depletion effect in smokers. There was no association between the plasma levels of these six micronutrients in women with cervical intraepithelial neoplasia and persistent human papillomavirus infection status in the placebo or the supplemented groups. Functional sequential nutrient interactions with each other or with other essential micronutrients and possible long-term toxicity need to be addressed in clinical trials.
The DNA content in oesophageal carcinoma and in sequential non-tumour mucosa was evaluated in 35 patients with oesophageal carcinoma, to explore the hypotheses that DNA distribution pattern and S-phase fraction can reflect malignant potential and that DNA aneuploidy can provide an early-warning signal of developing cancer. DNA flow cytometry was performed on 129 specimens from the tumours and on 119 specimens from non-tumour mucosa. Control specimens from gastric fundus had normal diploid DNA content and low S-phase fraction. Aneuploidy was found in 94.3% of the carcinoma specimens and intratumoral heterogeneity in 54.3%. Of the non-tumour specimens, 43.7% showed aneuploidy and none multiple aneuploidy. Pattern III distribution was present in 8.6% of the tumour specimens but not in non-tumour mucosa, where the incidence of aneuploidy rose with closeness to the tumour (p < 0.001). S-phase fraction was smaller in non-tumour than in tumour specimens (p < 0.0001). The study indicated that histologically tumour-free oesophageal mucosa may have a high malignant potential in patients with oesophageal carcinoma. The relative instability of such mucosa, with aneuploid cells and low S-phase fraction, may facilitate transition to abnormally proliferating cells in response to environmental signals. Cigarette smoking and alcohol may increase the risk of multicentric cancer development.
PURPOSE: We describe a murine model to evaluate variations of a published multicenter thyroid blocking protocol described for 131I antibody therapy, using doses of blocking agents proportional to those used in man. Variables include duration of super-saturated potassium iodide (SSKI) pretreatment and use of supplemental KClO4. MATERIALS AND METHODS: Whole-body activity measurements were performed 0, 24, 48 and 72 hours following 131I-NaI administration in control and thyroid-blocked mice. Retained whole-body activity was calculated as a percentage of the injected dose (%ID), primarily reflecting radioiodine sequestered in the thyroid gland. In blocked groups, SSKI was begun one or 7 days preceding 131I-NaI therapy, and was supplemented in one half of the cases with KClO4 from time of therapy. RESULTS: In control mice, %ID was 11.23 +/- 1.47%, 10.15 +/- 1.11% and 9.29 +/- 1.50% at 24, 48 and 72 hrs respectively. %IDs of blocked groups were markedly lower than controls (p = .0001). In the one day SSKI pretreatment group, %ID was reduced from 1.73 +/- 0.58, 1.42 +/- 0.45 and 1.20 +/- 0.38 at 24, 48 and 72 hours to 0.49 +/- 0.08, 0.50 +/- 0.07 and 0.44 +/- 0.06 with addition of supplemental KClO4. In the 7 day SSKI pretreatment group, %ID was reduced from 1.87 +/- 0.73, 1.48 +/- 0.49 and 1.36 +/- 0.57 at 24, 48 and 72 hours to 0.60 +/- 0.36, 0.45 +/- 0.13 and 0.41 +/- 0.14 with addition of supplemental KClO4. %IDs in the 7 day pretreatment animals were not statistically different from those in the one day pretreatment groups (all p >> 0.05). CONCLUSION: SSKI reduces retention of radioiodide approximately six-fold whereas supplemental KClO4 enhances thyroid blocking an additional three-fold. Seven day SSKI pretreatment appears no more effective than one day pretreatment.
The effect of subconjunctival retention of perfluoropropane (C3F8) gas on rabbit trabeculectomy was evaluated in this study to determine if this maneuver would increase the success rate of the surgery. Sixteen New Zealand white rabbits underwent trabeculectomy in the right eyes and trabeculectomy with subconjunctival retention of 0.3 mL C3F8 gas in the left eyes were used as animal models. One week and six weeks after the operations, the intraocular pressure (IOP) dynamics were compared between the two eyes after intravenous infusion of 0.9% NaCl sterile solution. The results showed that the average retention time of C3F8 gas within the subconjunctival space in the rabbits was 9.5 +/- 2.3 days. There were four parameters available in comparing IOP dynamics: Time Needed to Reach Peak IOP (TNRPI); Ascending Slope (AS); Peak IOP (PI) and Time Needed to Return to the Original IOP (TNROI). It was noted that at the 7th day after the operations, the IOPs in both eyes of the rabbits were not significantly increased after intravenous infusion of 0.9% NaCl solution. At the 42nd day, after 0.9% NaCl intravenous infusion, the eyes that had undergone trabeculectomy and subconjunctival retention of C3F8 gas had less IOP spiking than eyes that had undergone trabeculectomy alone (TNRPI: 6.7 +/- 2.2 vs. 4.2 +/- 2.9, p = 0.01, AS: 0.5 +/- 0.3 vs. 2.8 +/- 2.7, p = 0.002, PI: 24.4 +/- 9.6 vs. 18.7 +/- 7.4, p = 0.07 and TNROI: 6.8 +/- 5.8 vs. 14.7 +/- 11, p = 0.02). Our study suggested that subconjunctival retention of C3F8 gas increased the success rate of trabeculectomy in rabbits in the short-term follow-up period.
Insulin resistance and increased fat mass (FM) are common in human aging. We aimed to investigate the relationship between the age-dependent increase in FM and insulin resistance (by euglycemic hyperinsulinemic clamp technique), in a homogenous rodent model. The decline in insulin responsiveness was linear until late adulthood when body weight, FM, and epididymal fat reached a critical amount (r > .750, for all). Above this critical point, there was no further decline in insulin responsiveness with aging and with increased BW (p < .00001 for all spline curve analyses). This decline in insulin-mediated glucose uptake was accounted for by a decrease in whole body glycolytic rate with no change in the rate of glycogen synthesis. Thus, in this homogenous model, an early increase in FM is associated with impairment in insulin action until a critical FM is achieved, after which there is no additional insulin resistance with aging. We suggest that decreasing insulin responsiveness, in a heterogeneous group such as humans, will only occur within a specific accretion of visceral or total FM.
PURPOSE: The present study investigated the effects of noxious stimulation of the lower urinary tract on neuronal fos protein expression in the spinal micturition center of rats and also examined the effects of electroacupuncture (EA) on fos expression induced by noxious stimulation of the lower urinary tract. MATERIALS AND METHODS: Experiments were conducted on 21 female Sprague-Dawley rats divided into four groups. Group 1 rats (n = 5) served as normal controls. Group 2 rats (n = 5) received EA at the Sanyinjiao acupoint. Group 3 animals (n = 6) were catheterized through the urethra and instilled with 1% acetic acid, and group 4 (n = 5) animals received EA 1 hour before 1% acetic acid instillation. All animals underwent arterial perfusion, laminectomy, and spinal cord removal. Spinal cords were sectioned and processed for immunohistochemical staining for fos protein. RESULTS: No fos protein was detected in any spinal neurons in normal control animals, and either none or few (0 to 4 cells/section) fos-immunoreactive (fos-IR) cells were seen in animals treated with EA. Noxious stimulation of the lower urinary tract with 1% acetic acid drastically increased the number of fos-IR neurons (30 to 127 cells/L6 section, mean 76.17+/-13.98; 28 to 77, cells/S1 section, mean 59+/-8.30; 7 to 35 cells/S2 section, mean 19.83+/-4.10). However, EA administered 1 hour before 1% acetic acid instillation significantly decreased the number of fos-IR neurons resulting from chemical irritation (0 to 50 cells/L6 section, mean 19.8+/-9.33; 0 to 47 cells/S1 section, mean 13.2+/-9.12; 0 to 37 cells/S2 section, mean 13.6+/-7.31). CONCLUSIONS: Our study demonstrates that bladder instillation with 1% acetic acid induces fos protein expression in the spinal micturition center of the rat and that electroacupuncture can reduce this expression. These results suggest a link between electroacupuncture and reduction in spinal neuronal cell activity.
OBJECTIVE AND IMPORTANCE: Intraosseous schwannomas (neurilemomas) are rare neoplasms. In one large series, schwannomas accounted for less than 0.2% of all primary bone tumors. These schwannomas most commonly arise in the mandible and have also been observed, very rarely, in the vertebra. We present a patient with an unusual intraosseous schwannoma in the lumbar vertebra. CLINICAL PRESENTATION: A 58-year-old man who was admitted to Cathay General Hospital had complained of numbness and pain in his lower extremities for approximately 1 year. At the time of admission, a neurological examination revealed mild motor weakness and sensory numbness bilaterally in his lower legs. Magnetic resonance images showed a neoplastic lesion occupying the entire L4 body and the superior part of the L5 body, with marked perivertebral protrusion and compression of the thecal sac and bilateral neuroforamina. INTERVENTION: The patient underwent a computed tomography-guided needle biopsy and a two-stage operation. During the initial surgical procedure, the tumor mass was totally removed via an anterolateral approach. Fixation and fusion of the third to fifth lumbar vertebral bodies was accomplished using a full-thickness iliac bone graft with an anterior locking plate and screws. During the second operation, posterior fusion of L2, L3, L4, L5, and S1 with Luque wires and a Hartshill rectangle rod was performed to increase the spinal stability. CONCLUSION: Intraosseous schwannomas are rare neoplasms that are not commonly observed in the lumbar vertebral bodies. Schwannomas in the lumbar spine commonly originate from the nerve passing through the neural foramina. We report a rare case of L4 intraosseous schwannoma, the magnetic resonance imaging, computed tomographic, and histological findings, and the surgical procedures.
Spatially selective photocoagulation of subsurface-targeted blood vessels by repetitive application of a short cryogen spurt during continuous Nd:YAG laser irradiation has been demonstrated in two human cases. This procedure may be effective for the treatment of thick hemangiomas that require photocoagulation of subsurface blood vessels while protecting the epidermis.