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Biomedical subjects

C J Chang

Publications and source records attributed to C J Chang.

At least 163 records · Page 9Linked to original sources

Meliavolkenin, a new bioactive triterpenoid from Melia volkensii (Meliaceae).

Meliavolkenin, a new triterpene with an apotirucallane skeleton, has been isolated from the root bark of Melia volkensii (Meliaceae) by bioactivity-directed fractionation using the brine shrimp lethality test. The structure has been elucidated using spectral and chemical data. The relative stereochemistries were determined by reduction and acetonide derivations, and the ring conformations were analyzed using the results of NOESY experiments. Meliavolkenin was bioactive in the brine shrimp lethality test and gave moderate cytotoxicities against three human solid tumor lines.

Acetone↗

Clinical significance of urinary ferritin excretion in patients with transitional cell carcinoma.

1. The serum ferritin level provides a valuable index of the body iron store. An increase in serum ferritin has often been observed in patients with neoplastic disease and correlates well with the stage of cancer. A few studies have suggested the potential of urinary ferritin as a marker for transitional cell carcinoma. The rationale of the measurement, however, has not been investigated in detail. 2. Urinary ferritin levels were evaluated in patients with diverse urological diseases to investigate their potential clinical implications. 3. Analysis of logarithmic transformed values (ng/mg creatinine) showed that patients with both neoplastic and non-neoplastic urological diseases had significantly higher ferritin levels than normal control subjects (P = 0.02). There was no apparent difference between subgroups of patients with urological disease (P > 0.5). For patients with urothelial carcinoma, univariate analysis revealed a strong positive relationship between urinary ferritin levels and the density of lymphoid cells in tumour stroma (P = 0.0001), while no important association was observed with tumour grade (P = 0.32), stage (P = 0.29) or urinary cytology detection (P = 0.33). Patients with muscle-invasive tumour had significantly higher ferritin levels than those with papillary, superficial cancer (P < 0.05). For patients with non-neoplastic urological disease (n = 19), urinary ferritin levels tend to correlate with the severity of tissue inflammation (P = 0.03). 4. The results suggest that urinary ferritin may reflect the degree of local inflammatory reaction in the urinary tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Autoregulated induction of the acute-phase response transcription factor gene, agp/ebp.

AGP/EBP (C/EBP beta) is a key transcription factor responsible for transcriptional induction of many acute-phase protein genes. To characterize the regulation of this gene, we have isolated the mouse genomic DNA and sequenced the 5'-regulatory region. Using nuclear extracts from lipopolysaccharide (LPS)-stimulated or unstimulated mouse liver, three protein factor-binding motifs, UF1(-376 to -352), UF2(-254 to -223), and UF3(-220 to -190), as well as two Sp1 motifs (-309 to -277, and -264 to -241) were identified by DNase I footprinting assays. Biochemical analysis has shown that the AGP/EBP protein can bind to UF1 and UF2 sites, whereas an ubiquitous factor of unknown identity can bind to the UF3 site. Functional characterizations indicate that all of these factors play a major role in AGP/EBP induction. Thus, the agp/ebp gene is autoregulated during the acute-phase response.

Animals↗

Randomly amplified polymorphic DNA analysis of Xylella fastidiosa Pierce's disease and oak leaf scorch pathotypes.

Randomly amplified polymorphic DNA analysis was conducted with 14 primers to 17 strains of Xylella fastidiosa. There was a high degree of similarity among the seven Pierce's disease (PD) strains (Sxy > 0.93) and the seven oak leaf scorch (OLS) strains (Sxy > 0.96). However, the two groups were different, with a similarity index of 0.67, confirming the presence of a PD DNA cluster and suggesting the presence of a new OLS cluster. The control plum leaf scald strains (two strains) together with the periwinkle wilt strain had a much smaller similarity index (0.44) compared with the PD and OLS clusters.

Base Sequence↗

Decreased tobacco-glycoprotein-induced lymphocyte proliferation in vitro in pulmonary eosinophilic granuloma.

Pulmonary eosinophilic granuloma is a disorder caused by localized collections of proliferating histiocytes in the lung. Little is known about its etiology except that the majority (58 to 97%) of patients are current or ex-smokers, making the potential etiologic role of tobacco products an important area for research. Tobacco glycoprotein (TGP) is a potent immunostimulator that has been isolated from cigarette smoke. TGP-specific lymphocyte proliferation, and cytokine production in vitro, were measured in three patients with pulmonary eosinophilic granuloma in remission and in three closely matched normal subjects with similar smoking histories. One patient with eosinophilic granuloma of bone and a matched control subject were also studied. Peripheral blood mononuclear cells were cultured with TGP, the recall antigen streptokinase (SK), and the mitogen concanavalin A (Con A). All three of the patients with pulmonary eosinophilic granuloma exhibited significant decreases in lymphocyte stimulation to TGP, despite normal responses to SK and Con A. In contrast, the response of the patient with eosinophilic granuloma of bone was higher than her matched control. The mean responses of the patients with pulmonary eosinophilic granuloma to TGP was significantly lower than the mean of nondiseased smokers or of normal nonsmokers. Twenty-four-hour culture supernatants were collected and assayed for cytokine levels (IL-1, IL-2, and IL-6). TGP-stimulated IL-2 production was significantly lower in the patients with pulmonary eosinophilic granuloma than in the normal subjects, confirming the reduced T-cell proliferative response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus.

We examined the in vivo metabolic effects of vanadyl sulfate (VS) in non-insulin-dependent diabetes mellitus (NIDDM). Six NIDDM subjects treated with diet and/or sulfonylureas were examined at the end of three consecutive periods: placebo for 2 wk, VS (100 mg/d) for 3 wk, and placebo for 2 wk. Euglycemic hyperinsulinemic (30 mU/m2.min) clamps and oral glucose tolerance tests were performed at the end of each study period. Glycemic control at baseline was poor (fasting plasma glucose 210 +/- 19 mg/dl; HbA1c 9.6 +/- 0.6%) and improved after treatment (181 +/- 14 mg/dl [P < 0.05], 8.8 +/- 0.6%, [P < 0.002]); fasting and post-glucose tolerance test plasma insulin concentrations were unchanged. After VS, the glucose infusion rate during the clamp was increased (by approximately 88%, from 1.80 to 3.38 mg/kg.min, P < 0.0001). This improvement was due to both enhanced insulin-mediated stimulation of glucose uptake (rate of glucose disposal [Rd], +0.89 mg/kg.min) and increased inhibition of HGP (-0.74 mg/kg.min) (P < 0.0001 for both). Increased insulin-stimulated glycogen synthesis (+0.74 mg/kg.min, P < 0.0003) accounted for > 80% of the increased Rd after VS, and the improvement in insulin sensitivity was maintained after the second placebo period. The Km of skeletal muscle glycogen synthase was lowered by approximately 30% after VS treatment (P < 0.05). These results indicate that 3 wk of treatment with VS improves hepatic and peripheral insulin sensitivity in insulin-resistant NIDDM humans. These effects were sustained for up to 2 wk after discontinuation of VS.

Administration, Oral↗

Serum lipids and lipoprotein(a) concentrations in Chinese NIDDM patients. Relation to metabolic control.

OBJECTIVE: To compare serum blood lipids and lipoprotein(a) [Lp(a)] levels in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients and nondiabetic control subjects and also to determine the influence of diabetes control on serum Lp(a) concentration in Chinese individuals. RESEARCH DESIGN AND METHODS: We compared the serum blood lipids and Lp(a) levels in NIDDM patients (n = 100) and age- and sex-matched nondiabetic subjects (n = 100) who participated in a case-control study. Comparisons of Lp(a) concentrations were made between a normal control group, a group of diabetic patients with HbA1c < 8.0%, and a group of diabetic patients with HbA1c of 8% or higher. RESULTS: The diabetic patients had higher total triglyceride, apolipoprotein B (apo B), and apo B-to-apo AI ratios, but lower high-density lipoprotein (HDL) cholesterol and apo AI concentrations than nondiabetic controls (P < 0.001, P < 0.01, P < 0.001, P < 0.05, and P < 0.001, respectively). A similar pattern of distribution of Lp(a) levels according to the degree of metabolic control was seen in patients with NIDDM and nondiabetic controls. No correlation was observed between Lp(a) levels and total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, apo AI, apo B, and triglyceride levels in all diabetic patients. No difference in the Lp(a) levels was noted between diabetic patients and nondiabetic subjects, even in poorly controlled diabetic patients. CONCLUSIONS: In conclusion, Lp(a) levels are not elevated in diabetic patients, even in poorly controlled metabolic conditions.

Albuminuria↗

Presence of antitumor activities in the milk collected from gossypol-treated dairy cows.

Two human breast carcinoma cell lines (MCF-7, MCF-7 Adr) and a rat esophageal cancer cell line (RE-B2T) were used to evaluate the antiproliferative potential of gossypol (GP)-containing milk (GP-Milk), which was collected from Brown Swiss dairy cows treated daily with federally allowable 450 ppm of GP for 6 days. Treatment of the cultured cancer cells with GP-Milk for 24 h significantly inhibited the rates of 3H-thymidine incorporation during the ensuing 3-h period in all three tumorigenic cell lines. The inhibitory effects of GP-Milk occurred in a dose-dependent manner in all cases, but the calculated ED50 varied with cell lines. ED50 for GP-Milk was estimated at 10% for wild-type MCF-7 human breast cancer cells, 15% for multidrug-resistant MCF-7 Adr human breast cancer cells and 50% for RE-B2T rat esophageal carcinoma cells. The potential of GP-Milk as a dietary supplement for the prevention and/or treatment of human breast cancer is discussed in this paper.

Animals↗

Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice.

The physiological role of insulin-like growth factor (IGF) II (IGF-II) in adult humans is poorly understood. Rather high levels of IGF-II persist in adult human serum, whereas, in rodents, IGF-II levels are very low. To investigate the physiological and carcinogenic effects of persistently elevated IGF-II in adults, we have produced two lines of transgenic mice in which high levels of IGF-II (20- or 30-fold increase above normal) are persistently maintained in the blood. The transgene is driven by the major urinary protein promoter, and it is highly expressed in the liver and perputial glands in both lines. The adult transgenic mice are smaller than controls, and their body composition is altered. Their lean body mass is reduced by 5-8%, whereas fat mass is reduced between 44 and 77%. The mice expressing the highest level of IGF-II (30x) develop hypoglycemia and hypoinsulinemia and IGF-I levels are normal. Mice in the lower expression line (20-fold elevated IGF-II) develop hypoglycemia progressively over their lifetime. Mice from both lines also develop a diverse spectrum of tumors at a higher frequency than controls after 18 months of age, and the most frequent types of tumors are hepatocellular carcinomas and lymphomas. Squamous cell carcinoma, sarcoma, and thyroid carcinomas also occurred in our test group. The long latent period before tumors arise and the wide spectrum of tumor types suggest that IGF-II may function primarily as a tumor progression factor in mice via autocrine and endocrine mechanisms of action.

Animals↗

The use of severe combined immunodeficiency mice to study the metabolism of human immunoglobulin G.

BACKGROUND: Although the four human immunoglobulin G (IgG) isotypes are similar in structure, they exhibit significant differences in effector function and catabolic half-life. With advent of structurally engineered antibodies, there is the potential to design antibody constructs with desired half-lives; however, it is first necessary to discover the structures and mechanisms that control immunoglobulin metabolism. METHODS: Radioiodinated chimeric antibodies, consisting of a mouse antidansyl variable region and the four human IgG constant regions, were injected intravenously into Balb/c and severe combined immunodeficiency (SCID) mice, and their half-lives were determined by whole body and whole blood counting. Dependence of the rate of immunoglobulin catabolism on immunoglobulin concentration, a normal regulatory phenomenon specific to IgG, was evaluated by the introduction of large amounts of human gamma-globulin intraperitoneally. RESULTS: Whole body and blood half-lives were statistically indistinguishable. The four IgG isotypes were eliminated from the whole animals in a predominantly single-phasic manner, with the half-life being dependent on the isotype studied. In Balb/c mice, immune elimination frequently occurred after 6 days, although this was not observed in SCID mice. Relevance of the model was confirmed by the demonstration of the presence of the concentration-catabolism phenomenon, a relationship unique to normal IgG regulation. CONCLUSIONS: SCID mice provide an adequate initial animal model for the study of human-mouse chimeric antibodies. Further understanding of the factors governing immunoglobulin catabolism can be probed by study of recombinant human constant regions in this animal system.

Animals↗

An assessment of immunoreactive epidermal growth factor in urine of patients with urological diseases.

To examine the excretion of urinary epidermal growth factor (EGF) in urological diseases and the relationship of EGF urine levels with transitional cell carcinoma (TCC), we measured the concentration of EGF by radioimmunoassay. The series comprised patients with active TCC (n = 52), others in tumor-free status (n = 29) and with non-neoplastic inflammatory diseases (n = 43), and normal controls (n = 50). Urinary EGF values were lower in patients with urological diseases of different etiologies than in normal controls (P < 0.005). Mean EGF levels of patients who had previous bladder tumor resection (n = 21) were not statistically different from normal controls (P = 0.2). For patients with active TCC, EGF urine levels showed a significant inverse relationship to increasing tumor grade (P = 0.02). In addition, subjects who had received nephrectomy for pelvic carcinoma (n = 8) showed significantly lower mean EGF values than those with intact kidneys (n = 21), irrespective of sex (P < 0.05). Immunostaining of EGF on non-neoplastic kidney (n = 9) revealed reactivity in the distal convoluted tubules and thick ascending limbs of Henle. Our results suggest that the kidney is the major source of urinary EGF. Its excretion in urine is decreased in both inflammatory and neoplastic diseases of the urinary tract. EGF may play an important part in the biological activity of TCC. Further study is indicated to investigate the monitoring of EGF urine levels as a marker of recurrence for EGF receptor-positive TCC.

Adult↗

Recovery of epinephrine response but not hypoglycemic symptom threshold after intensive therapy in type 1 diabetes.

PURPOSE: Patients with intensively treated insulin-dependent diabetes mellitus (IDDM) exhibit more severe defects in counterregulatory hormone secretion and symptom recognition during hypoglycemia than do conventionally treated patients. In this prospective study in patients with preexisting defects in counterregulation, we examined the induction and reversibility of impaired symptomatic and adrenomedullary responses to hypoglycemia in 5 patients with IDDM (diabetes duration of 2 to 16 years; aged 19 to 36 years; 3 women, 2 men) who were receiving intensive therapy. METHODS: Counterregulatory responses were assessed by using a single-step (approximately 2.8 mmol/L plasma glucose) and multiple-step (from approximately 5 mmol/L to 2.2 mmol/L plasma glucose) clamped hypoglycemia procedure. Patients were first studied after a stable period of conventional insulin therapy (glycosylated hemoglobin [HbA1c] 9.5 +/- 1.2%), then after 3 to 5 months of intensive therapy (HbA1c 6.6 +/- 0.2%), and a third time after resuming conventional therapy (HbA1c 8.7 +/- 0.9%). RESULTS: Intensive therapy was associated with a 44% decline (P < 0.01) in the average plasma epinephrine increase during hypoglycemia, and the plasma glucose level required to stimulate epinephrine secretion fell from 3.7 +/- 0.2 to 3.0 +/- 0.1 mmol/L (P < 0.01). The threshold, but not the magnitude, of the plasma norepinephrine response was similarly altered. Hypoglycemic symptoms also decreased in intensity (by 67%, P < 0.01), and the glucose level required for symptom activation fell from 3.4 +/- 0.3 to 2.7 +/- 0.2 mmol/L, P < 0.01). When conventional therapy was resumed, the abnormalities in the epinephrine response due to intensive therapy were almost completely reversed. However, the reduction in symptoms and the altered thresholds for plasma norepinephrine were not reversed. CONCLUSIONS: There is dissociation between the treatment-associated defects in hypoglycemia counterregulation in IDDM, and an increase in average glycemia produced by a return to conventional insulin therapy is not sufficient to reverse hypoglycemia unawareness worsened by intensive therapy.

Adult↗

Determination of taxanes in Taxus brevifolia extracts by tandem mass spectrometry and high-performance liquid chromatography.

A tandem mass spectrometric (ms/ms) method using desorption chemical ionization is described for the quantitation of taxol [1], cephalomannine [2], and baccatin III [3] found in Taxus brevifolia bark and needle extracts. A parent ion scan was used to simultaneously determine the weight percentages of 1-3 in bark and needle samples by the method of standard addition. In an alternative experiment, the concentration of 1 in the same samples was determined by ms/ms using trideuterated 10-acetyltaxol [7a] as an internal standard. High-performance liquid chromatography (hplc) was also used to determine the weight percentages of 1-3 in the same T. brevifolia bark and needle extracts with an external standard. The ms/ms method of quantitation by internal standard is the best overall method of analysis examined. With this method, 1 was quantitated in the T. brevifolia extracts at the low picomole level with a relative standard deviation of 17% or better for all samples analyzed with an analysis time of less than five min per sample. The precision, level of quantitation, and speed of analysis of the three methods of taxane quantitation are compared.

Alkaloids↗

Cytotoxic cyclolignans from Koelreuteria henryi.

Chemical investigation of the cytotoxic fraction of Koelreuteria henryi resulted in the isolation of three cyclolignans. A new cyclolignan, named koelreuterin-1 was elucidated as furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(8H)-one,5-(7-methoxy-1, 3- benzodioxol-5-yl)[1]. Two known cyclolignans were characterized as austrobailignan-1 [2] and austrobailignan-2 [3]. The structure elucidation of 1 was based on extensive 1H- and 13C-nmr spectral analyses. Further chemical conversion of 2 to 3 and oxidative transformation of 2 to 1 unambiguously confirmed the structure of 1. The cytotoxicity and tubulin polymerization inhibitory activity of 1-3 are discussed.

4-Butyrolactone↗

The role of tobacco, alcohol use, and body mass index in oral and pharyngeal cancer.

BACKGROUND: Although tobacco smoking and alcohol drinking are well-established risk factors for oral cancer, relatively few studies have addressed the comparative effect of filter versus non-filter cigarettes, the nature of the reduction in risk following cessation, and the joint effects of tobacco and alcohol. In addition, recent studies suggest an inverse association of body mass index with oral cancer. We used data from a large, hospital-based case-control study to investigate these issues. METHODS: The data set consisted of 1097 male and 463 female oral cancer cases and 2075 male and 873 female controls. Unconditional logistic regression was used to estimate the effect of risk factors in the presence of covariates. RESULTS: Among male current smokers, users of filter cigarettes (whether lifetime users or those who switched to filter cigarettes) had a significantly reduced risk of oral cancer which approached 50%. Among female current smokers, only those who switched to filter cigarettes 10+years previously showed a significantly reduced risk. Those who quit smoking experienced a marked decrease in risk compared to current smokers. Smoking and alcohol consumption showed a significant interaction on a multiplicative model. After adjustment for covariates, leanness was significantly associated with oral cancer among male current and ex-smokers. CONCLUSIONS: The results of this study: 1) indicate that smokers of filter cigarettes and those who quit smoking are at substantially reduced risk of oral cancer, 2) demonstrate interaction between smoking and drinking, and 3) suggest that leanness preceding diagnosis may be associated with oral cancer.

Adult↗

A 12-month study of the effects of oral zidovudine on neurodevelopmental functioning in a cohort of vertically HIV-infected inner-city children.

OBJECTIVE: To examine the effects of oral zidovudine on the neurodevelopmental functioning of HIV-infected children. METHODS: Oral zidovudine was administered to 54 symptomatic children with vertically transmitted HIV infection (Centers for Disease Control and Prevention class P2). All children were recruited from an inner-city pediatric HIV/AIDS outpatient clinic and ranged in age from 2 months to 12 years and 11 months (mean age, 3 years) at entry. Neurodevelopmental functioning, height and weight, and lymphocyte subpopulation data were ascertained for all the children pretherapy, and 6 and 12 months post-therapy initiation. RESULTS: Analysis of the 6- and 12-month post-initiation drug data found no significant change in neurodevelopmental functioning. Height and weight percentiles remained the same or improved in the majority of children. CD4+ cell counts declined over the treatment period with CD4+ counts < 500 x 10(6)/l observed in 15% of the children pre-therapy, and 33% after 1 year. CONCLUSION: In contrast with previously published data, the present study observed no improvement in neurodevelopmental functioning in HIV-infected children treated with oral zidovudine.

Black or African American↗

Maxillary involvement in central craniofacial fractures with associated head injuries.

From January 1983 through December 1990, we treated 703 patients with central craniofacial fractures. Among them 177 had maxillary fractures, with or without frontonasoethmoidal involvement. Of the 177, 151 patients were diagnosed in the acute stage. Using the Glasgow Coma Scale, these 151 patients were divided into three groups: group I (GCS score 13-15), 100 patients; group II (GCS score 9-12), 33 patients; group III (GCS score 3-8), 18 patients. The patterns of facial fractures were analyzed and surgically corrected after the following average postadmission lags: group I, 7.1 days; group II, 11.5 days; group III, 13.3 days. The average hospital stay for each group was: group I, 15.6 days; group II, 19.5 days; and group III, 27.2 days. The mean follow-up period was 12 months. The physiologic, functional and esthetic outcomes were assessed. Regardless of initial head injury severity, the outcomes in each group showed almost no statistically significant differences, and unnecessary extended hospital stays may be avoided by early surgical management.

Adolescent↗

The osmotic lysis of Spiroplasma cells and its use in enzyme studies.

A simple and efficient osmotic lysis method was developed for enzyme studies in spiroplasmas. Log phase cells in R2 medium were harvested by centrifugation (19,600 x g for 30 min). Wash buffer supplemented with 0.23 M sucrose maintained the helicity of spiroplasma cells during washing. Osmotic lysis of spiroplasmas was achieved in H buffer that contained no sucrose. Sucrose at concentrations as low as 0.004 M dramatically increased the resistance of the spiroplasmas to osmotic lysis. NADH oxidase, lactate dehydrogenase, and malate dehydrogenase were detected in cell lysates of Spiroplasma floricola (23-6), Spiroplasma citri (R8A2), Spiroplasma apis (SR 3), and Spiroplasma melliferum (AS 576). Citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl coenzyme A synthetase, succinate dehydrogenase, and fumarase were not detected in cell lysates of S. floricola (23-6). NADH oxidase and malate dehydrogenase were found in the cytosol whereas lactate dehydrogenase was loosely associated with the cytomembrane.

Bacteriolysis↗