PubMed HealthSearch

Biomedical subjects

C J Chang

Publications and source records attributed to C J Chang.

At least 19 recordsLinked to original sources

Natural history of cervicovaginal papillomavirus infection in young women.

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.

Adult

Effects of en bloc esophagectomy on nutritional and immune status in patients with esophageal carcinoma.

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.

Aged

Effect of prior hepatitis B infection on serum IgE levels in patients with human immunodeficiency virus infection.

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.

CD4-CD8 Ratio

Plasma concentrations of micronutrients during a nine-month clinical trial of beta-carotene in women with precursor cervical cancer lesions.

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.

Adult

The effect of age-dependent increase in fat mass on peripheral insulin action is saturable.

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.

Adipose Tissue

Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells.

Fourteen structurally diverse Annonaceous acetogenins, representing the three main classes of bis-adjacent, bis-nonadjacent, and single-THF ring(s), were tested for their ability to inhibit the growth of adriamycin resistant human mammary adenocarcinoma (MCF-7/Adr) cells. This cell line is resistant to treatment with adriamycin, vincristine, and vinblastine and is, thus, multidrug resistant (MDR). Among a series of bis-adjacent THF ring acetogenins, those with the stereochemistry of threo-trans-threo-trans-erythro (from C-15 to C-24) were the most potent with as much as 250 times the potency of adriamycin. A spacing of 13 carbons between the flanking hydroxyl of the THF ring system and the gamma-unsaturated lactone seems to be optimum with a spacing of 11 and 9 carbons being significantly less active. Several single-THF ring compounds were also quite potent with gigantetrocin A (11) being the most potent compound tested. The acetogenins may, thus, have chemotherapeutic potential, especially with regard to MDR tumors.

Adenocarcinoma

Concordance of positive and negative symptoms in coaffected sib-pairs with schizophrenia.

Positive and negative symptom (NGS) dimensions were examined for their concordance in 46 coaffected schizophrenic sib-pairs. Results showed that the symptom dimensions of negative symptoms (NGS), delusion-hallucination (DHS), and thought disorganization (TDS) could be formulated. Discrete genetic endowment of these three symptom dimensions was not found as shown by the low concordance in sib pair analysis (kappa = 0.20-0.30). Thirty-seven pairs (80.4%) and 21 pairs (45.7%) had liability, defined by the presence of NGS in any one member of the coaffected sib-pairs, of NGS of "any degree", and of "severe degree" in 46 sib-pairs, respectively. Both groups had high prevalence (59.1-81.0%) of positive symptoms. Another 9 (19.6%) and 25 (54.3%) pairs had no liability of NGS of "any degree" or of "severe degree" out of 46 sib-pairs, respectively. These two groups had high concordance (kappa = 0.45-1.00) of TDS or DHS between coaffected sib-pairs. Based on the results, it is hypothesized that schizophrenia, as defined by DSM-III-R, may consist of two subtypes: one has liability of NGS and a high prevalence of positive symptoms, while the other has only positive symptoms.

Delusions

Unscheduled DNA replication precedes apoptosis of photoreceptors expressing SV40 T antigen.

Expression of simian virus 40 T antigen (Tag) in the rod photoreceptors of transgenic mice leads to cell death that is completed by the end of the third week of postnatal development. To understand the mechanistic link between Tag expression and the death of the expressing photoreceptors, cell cycle activity was followed in a transgenic mouse family that expresses Tag directed by the mouse opsin promoter. Tag-expressing photoreceptors also expressed rhodopsin suggesting that these cells were differentiated. The presence of Tag in the photoreceptors induced the expression of both proliferating cell nuclear antigen (PCNA) and thymidine kinase (TK). The abnormally high levels of PCNA and TK continued until the complete disappearance of the cells expressing Tag. Photoreceptor cell death was also associated with continued DNA synthesis that ceased shortly after postnatal day 16. The specific loss of the rod photoreceptors that re-entered the cell cycle accounted entirely for the loss of photoreceptors from the outer nuclear layer. The antiproliferative nature of the mature retina is directly involved in the apoptotic death of photoreceptors expressing Tag.

Animals

Effects of beta-carotene and other factors on outcome of cervical dysplasia and human papillomavirus infection.

Women with histopathologically confirmed cervical intraepithelial neoplasia (CIN) were followed at 3-month intervals in a randomized double-blinded trial to evaluate the efficacy of beta-carotene to cause regression of CIN. Questionnaire data, plasma levels of micronutrients, and a cervicovaginal lavage for human papillomavirus (HPV) detection were obtained at each visit, and an endpoint biopsy was performed at 9 months. Sixty-nine subjects had a biopsy endpoint evaluation; 9 of 39 (23%) subjects in the beta-carotene group versus 14 of 30 (47%) in the placebo group had regression of CIN (P = 0.039). Independent risk factors for persistent CIN at 9 months included type-specific persistent HPV infection (OR = 11.38, P = 0.006) and continual HPV infection with a high viral load (OR = 14.25, P = 0.007) at baseline and 9 months, an initial diagnosis of > or =CIN II (OR = 6.74, P = 0.016), and older age (OR for > or =25 years = 4.10, P = 0.072). After controlling for these factors, the beta-carotene and placebo groups did not differ in risk for having CIN at 9 months (OR = 1.53, P = 0.550). Resolution of baseline HPV infection was significantly correlated with non-high-risk HPV types (RR = 2.94, P = 0.015), age <25 years (RR = 2.62, P = 0.014), and douching after sexual intercourse (RR = 3.02, P = 0.012), but not with randomization group. Our data indicate that a large proportion of mild CIN lesions regress; age and HPV infection play an important role in the natural course of CIN; and repeated HPV testing may have a value in distinguishing women who need aggressive treatment for CIN versus those who do not. Supplementation of beta-carotene does not appear to have a detectable benefit in treatment of CIN.

Adult

Contrasting effects of identical nutrients given parenterally or enterally after 70% hepatectomy: bacterial translocation.

High mortality occurs in rats with 70% hepatectomy fed intravenous (IV) total parenteral nutrition (TPN; 13.9% glucose, 4.17% amino acids, 1.46% fat, electrolytes, trace minerals, and vitamins providing 216 kcal.kg-1.d-1) but not when the identical nutrients are given at the same rate enterally (gastrostomy). We hypothesized that a difference in bacterial translocation (BT) was a contributing factor to this phenomenon. Forty-five male Sprague-Dawley rats (300-360 g) were divided into five groups and underwent the following: control (no operation), sham (intraperitoneal [IP] pentobarbital anesthesia, central venous and gastrostomy catheters, laparotomy, sham hepatectomy), standard oral feeding (SOF), TPN (IV nutrients), and total enteral nutrition (TEN; gastrostomy). The SOF, TPN, and TEN groups had IP pentobarbital anesthesia, central venous and gastrostomy catheters, and 70% hepatectomy. Postoperatively, control and SOF (both catheters plugged) rats ate a commercial rat chow and drank tap water ad libitum pre- and postoperatively. The sham, TPN, and TEN groups were given the identical infusate composition as above, but the nutrient concentrations were cut in half (110 kcal/kg) and three-quarters (165 kcal/kg) on postoperative days 1 and 2, respectively. At the end of postoperative day 2, all rats were euthanized. BT to mesenteric lymph nodes (MLNs), liver, spleen, and lungs was significantly higher in the TPN rats compared with all other groups, except that BT to the MLNs was similar in the TPN and TEN groups. Bacteremia was found only in the TPN rats. BT in TPN rats with 70% hepatectomy was significantly greater 48 h after operation than in those fed the identical nutrients enterally at the same rate; this correlates with the previously reported significantly greater mortality in rats with 70% hepatectomy receiving TPN.

Animals

Multidrug-resistance modulators from Stephania japonica.

An alkaloidal extract of the vines of Stephania japonica showed multidrug-resistance-reversing activity as demonstrated by the bicinchoninic acid assay. Two known bisbenzylisoquinoline alkaloids, isotrilobine (1) and trilobine (2), were isolated by bioassay-directed fractionation and separation. Isotrilobine (1) was shown to be as active as verapamil (3) in reversing doxorubicin resistance in human breast cancer cells.

Antineoplastic Agents, Phytogenic

Transcriptional induction of the agp/ebp (c/ebp beta) gene by hepatocyte growth factor.

Hepatocyte growth factor (HGF) is a pleiotropic factor with mitogenic, morphogenic, motogenic, cytotoxic, or growth inhibitory activity. Although the signaling of HGF is mediated through the cell membrane receptor c-Met, the molecular mechanism of downstream signal transduction remains obscure. In this report, we present evidence that shows HGF can stimulate the expression of AGP/EBP (C/EBP beta) and NF-kappaB, which are both key transcription factors responsible for the regulation of many genes under stress conditions or during the acute-phase response. Biochemical and functional analysis indicates that the HGF-responsive element is located in the region -376 to -352 (URE1) of the 5'-upstream regulatory sequence of agp/ebp. Activation of NF-kappaB by HGF was observed to precede the induction of agp/ebp. Further studies indicate that NF-kappaB can cooperate with AGP/EBP or other members of the C/EBP family to activate the agp/ebp gene in both URE1 and URE2-dependent manner. These results suggest that the induction of the agp/ebp gene by HGF is mediated at least in part by its activation of NF-kappaB. The activated NF-kappaB then interacts with AGP/EBP, resulting in the induction of agp/ebp.

Animals

Reconstruction of head and neck hemangiomas with tissue expansion in the pediatric population.

A retrospective study of 245 patients with 299 hemangiomas treated from May 1981 to April 1994 was done. A subset of 175 of these patients (58.5%) had hemangiomas of the head and neck. Six of the 175 (3%) required reconstruction following laser therapy. Tissue expansion was chosen for each of these reconstructions. Five females and 1 male underwent tissue expansion. The age of the patients at the time of tissue expansion ranged from 2.5 to 12 years, with an average of 6 years. Tissue expander sizes were 50 cc and 100 cc. Infection was seen during the course of expansion in 1 patient. Satisfactory results were achieved after reconstruction in all cases. Tissue expansion is the treatment of choice for reconstruction of head and neck hemangioma deformities following laser or other surgical procedures as well as involution.

Child

Management of hemangioma of infancy: review of 245 patients.

A retrospective study of patients treated from May of 1981 to April of 1994 was conducted. A total of 245 patients with 299 hemangiomas were studied, which represents the largest series reported to date. The study consisted of 173 females and 72 males ranging in age from 1 day to 59 years, with the average age being 4 years and 7 months. Twenty-six were premature neonates (14 females and 12 males). An interesting finding was a 1:1 sex ratio among this group in contrast to the 3:1 female-male ratio frequently reported in the literature. Onset was at birth in 170, within the first month in 43, and after the age of 1 month in 32 patients. Among the 245 patients, 175 hemangiomas were located on the head and neck, 62 on the trunk, 49 on the extremities, and 13 in the perineal area. Five groups of patients were defined based on clinical management. As a result, these groups are not similar. The five groups are as follows: group I (48), observation; group II (9), steroid treatment; group III (27), excision and reconstruction; group IV (88), laser therapy; and group V (73), combined therapy. The involved area of hemangioma was as follows: group 1, 0.5 x 0.5 to 20 x 8 cm; group II, 2 x 2 to 8 x 8 cm; group III, 0.4 x 0.8 to 7 x 7 cm; group IV, 0.5 x 0.5 to 20 x 9 cm; and group V, 1.5 x 1.5 to 25 x 25 cm. The complications of hemangioma seen at the time of consultation were obstruction (28.6 percent), ulceration (20.4 percent), bleeding (14.7 percent), infection (4.9 percent), and pain (0.4 percent). Treatment periods ranged from 1 month to 11 years, with the mean period in each group as follows: group I, 4 years and 9 months; group II, 2 years and 5 months; group III, 1 year and 1 month; group IV, 2 years and 1 month; and group V, 3 years. The outcomes of each patient were evaluated based on improvement of volume, color, and texture by the following scale: 1, poor (0 to 25 percent); 2, fair (26 to 50 percent); 3, good (51 to 75 percent); and 4, excellent (76 to 100 percent). Each of these parameters was summarized for each of the five groups. Statistical analysis by the Irwin-Fisher test was used for analysis and comparison of the final results between groups. Statistically significant differences in outcomes between treatment groups were demonstrated. Laser therapy was shown to be statistically superior to observation with regard to length of treatment and with regard to outcomes of volume and texture (p < 0.05).

Adolescent

PCR detection of human papillomavirus: comparison between MY09/MY11 and GP5+/GP6+ primer systems.

Human papillomavirus (HPV) is an etiologic agent of cervical cancer and is the most common sexually transmitted disease in women. PCR amplification of HPV genomes is the most sensitive method for the detection of cervicovaginal HPV. We have compared the two most commonly used PCR primer sets, MY09/MY11 (MY-PCR) and GP5+/GP6+ (GP+-PCR), for the detection of HPV DNA in cervicovaginal lavage samples from 208 women. Oligonucleotide probes for 39 different HPV types were used. Both primer sets amplified a wide spectrum of HPV genotypes and detected similar overall prevalences of 45% (94 of 208) and 43% (89 of 208), respectively. The MY-PCR system detected 27 of 30 (90%) samples with multiple HPV types, whereas the GP+-PCR system detected 14 of 30 (47%) samples with multiple HPV types. Differences in the detection of HPV types 35, 53, and 61 were noted between the two primer systems. Serial dilution of plasmid templates indicated a 3-log decrease in the amplification of HPV type 35 by MY-PCR and HPV types 53 and 61 by GP+-PCR. These results indicate that although the MY-PCR and GP+-PCR identified nearly equivalent prevalences of HPV in a set of clinical samples, differences in the detection of specific types and infections with multiple types were found. Differences in the sensitivities and characteristics of the PCR systems for the detection of HPV within clinical samples should be considered when comparing data between studies and/or in designing new studies or clinical trials.

DNA Primers

Identification and characterization of a nucleolar phosphoprotein, Nopp140, as a transcription factor.

Expression of the alpha-1 acid glycoprotein (AGP) gene (agp) is activated by a key transcription factor, AGP/enhancer-binding protein (AGP/EBP, commonly called C/EBP beta), in the liver during the acute-phase response. In addition to this positive regulation, agp is negatively regulated by nucleolin (T. H. Yang et al., Mol. Cell. Biol. 14:6068-6074, 1994). Other factors involve in positive regulation of the agp gene are poorly characterized. In a systematic search for factors that may interact with AGP/EBP, we have identified Nopp 140, a phosphoprotein of 140 kDa, by immunoaffinity chromatography. Nopp 140 not only functions as a transcriptional activator per se but also interacts with AGP/EBP to synergistically activate the agp gene in an AGP/EBP-binding motif-dependent manner. In addition to interacting with AGP/EBP, Nopp140 interacts specifically with TFIIB. Distinct regions of Nopp140 that interact with AGP/EBP and TFIIB have been characterized. The sequence of Nopp140 contains several stretches of serine- and acidic amino acid-rich sequences which are also found in ICP4 of herpes simplex virus type 1, a known transcription factor that interacts with TFIIB. The physical interaction between TFIIB and wild-type Nopp140 or several deletion mutants of Nopp140 correlates with the ability of Nopp140 to activate the agp gene synergistically with AGP/EBP. Thus, the molecular mechanism for agp gene activation may involve the interaction of AGP/EBP and TFIIB mediated by coactivator Nopp140.

Amino Acid Sequence