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Biomedical subjects

H R Chang

Publications and source records attributed to H R Chang.

At least 37 records · Page 2Linked to original sources
PubMed1997

Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii.

The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery.

Acute Disease↗
PubMed1996

Reduction in lymphocyte beta-adrenergic receptor density in infants and children with heart failure secondary to congenital heart disease.

To identify changes in catecholamine levels and beta-adrenergic receptor density in children with varying degrees of congestive heart failure, we measured plasma norepinephrine (NE), epinephrine, and beta-adrenergic receptor levels in 91 noncyanotic patients using high-performance liquid chromatography and a radioligand binding assay. Plasma NE levels in 41 patients with heart failure (694 +/- 236 pg/ml) were significantly higher than those in 50 patients without it (274 +/- 68 pg/ml, p < 0.001). In addition, beta-adrenergic receptor density was significantly lower in patients with heart failure (0.81 +/- 0.48 fmol/10(6) cells) than in those without it (2.43 +/- 1.09 fmol/10(6) cells, p < 0.001), but epinephrine levels were not significantly different between the 2 groups. The receptor reduction in heart failure correlated well with elevated plasma NE levels (r = -0.60, p < 0.001). The degree of left to right shunt flow and pulmonary systolic pressure correlated directly with plasma NE levels and inversely with beta-adrenergic receptor density. From the best compromise between sensitivity and specificity, the optimal cutoff point for heart failure was > 390 ng/ml for NE and < 1.30 fmol/10(6) cells for beta-adrenergic receptor density, respectively. A follow-up study in 15 of 30 patients with heart failure after surgery showed a significant decrease in plasma NE and an increase in beta-adrenergic receptor density. Changes in plasma NE levels and beta-adrenergic receptor density occur concurrently with clinical symptoms of heart failure and may be used as indexes for assessing the presence and severity of heart failure in infants and children.

Adolescent↗
PubMed1996

Younger women with breast carcinoma have a poorer prognosis than older women.

BACKGROUND: It is controversial whether breast cancer in young women is more aggressive than in older women. This study was initiated to determine age-associated outcome of women with breast carcinoma. METHODS: Patients with breast carcinoma, who were identified in a statewide tumor registry, were divided into age groups based on 10-year intervals (ages 40 and younger, 41 to 50, 51 to 60, 61 to 70, 71 to 80, and older than 80 years). Age at diagnosis, American Joint Committee on Cancer classification, 5-year disease free (5DFS) and cancer specific (5CSS) survival estimates using Kaplan-Meier analysis were determined. RESULTS: Between 1985 and 1992, 3722 women were diagnosed with invasive breast carcinoma. Approximately 5.6% (210) of the women were 40 years old or younger. The youngest age group had the worst 5CSS of 69.7%, followed by the oldest age group (> 80, 5CSS = 71.45%). The age groups 41 to 50, 51 to 60, 61 to 70, and 71 to 80 years had 5CSS of 80.30%, 78.45%, 82.06%, and 84.27%, respectively. The oldest age group (> 80) had the worst 5DFS (39.88%) followed by the youngest age group (< or = 40, 5DFS = 60.79%). The age groups 41 to 50, 51 to 60, 61 to 70, and 71 to 80 years had 5DFSs of 73.22%, 66.87%, 71.53%, and 63.11%, respectively. Analyzed by stage, young (< or = 40 years) women had a worse 5CSS when compared with the other age groups, except for those with Stage I disease. CONCLUSIONS: Our results indicate that women 40 years of age and younger have a worse 5CSS than their older counterparts. This difference in survival is not solely a reflection of more advanced disease but may reflect differences in tumor biology.

Adult↗
PubMed1996

Lymphocyte beta2-adrenergic receptors and plasma catecholamine levels in lead-exposed workers.

The effect of lead exposure on beta2-adrenoceptor density and catecholamine response was studied in 26 male workers and 1 female worker, exposed to lead on average for 6 years. The systolic blood pressure in lead workers (101-160 mmHg, 124.4 +/- 14.7 mmHg) was found to be significantly higher than in controls (97-134 mmHg, 115.4 +/- 10.4 mmHg, p < 0.01) as was plasma norepinephrine (0.51 +/- 0.1 microg/liter vs 0.24 +/- 0.05 microg/liter, p < 0.01). The density of lymphocyte beta2-adrenergic receptors (Bmax) in lead-exposed workers was 86% lower than that in controls (0.15 +/- 0.08 vs 1.08 +/- 0.29 fmol/0.1 x 10(6) cells; p < 0.01). The dissociation constants (Kd) of [125I]iodocyanopindolol were 93.6 +/- 42.6 and 87.9 +/- 42.7 pM in lead-exposed workers and controls, respectively. Multiple linear regression analysis showed that elevation of systolic pressure was closely related to (a) blood lead levels, (b) decreased beta2-adrenergic receptor density, and (c) increased plasma catecholamine levels in lead-exposed workers. Linear regression analysis revealed that both plasma norepinephrine levels and beta2-adrenoceptor density (Bmax) were highly correlated with both systolic blood pressures and blood lead levels in lead-exposed workers, and a highly significant negative correlation was found to exist between Bmax and plasma norepinephrine levels (r = -0.82, p < 0.001). These data therefore demonstrate that there is a close relationship between elevated plasma catecholamine levels, decreased beta2-adrenergic receptors, and elevated blood pressure in lead-exposed workers.

Adult↗
PubMed1996

Circulating noradrenaline and beta-adrenergic receptors in children with congestive heart failure.

This study was designed to investigate changes in plasma catecholamine concentrations and the number of beta-adrenoceptors (beta-AR) of circulating lymphocyte in 94 noncyanotic congenital heart patients. In 43 patients with congestive heart failure, beta-AR density was significantly lower (p < 0.001) and plasma noradrenergic levels were significantly higher (p < 0.001) compared with corresponding values in 51 patients without heart failure. A significant negative correlation between lymphocyte beta-AR density and plasma noradrenergic levels was observed (r = -0.61, p < 0.001). The degree of left-to-right shunt and pulmonary pressure was correlated directly with noradrenaline level and inversely with lymphocyte beta-AR density. Both plasma noradrenaline level and lymphocyte beta-AR density return to normal in children with heart failure after surgical repair. Our results support the idea that changes in noradrenaline level and lymphocyte beta-adrenoceptor density occur concurrently with the presence and severity of heart failure in children.

Adolescent↗
PubMed1996

Simple HPLC determination of the concentrations of epiroprim in the serum and brains of mice.

Epiroprim, an analogue of trimethoprim, has been shown to potentiate the efficacy of dapsone in experimental parasitic infections. A simple and accurate HPLC method has been developed to estimate epiroprim in serum and brain. Blood and brains from mice were sampled 0, 30, 75, 120 and 240 min after 50 or 100 mg kg-1 oral gavage. The drug and added internal standard metoprine in serum and brain supernatant were isolated by solid-phase extraction (Superclean LC-SCX). The HPLC system consisted of a 150 x 4.6 mm Hypersil 5 microns ODS column. The mobile phases contained various proportions of acetonitrile, methanol and phosphate buffer (0.1 M). Peaks were detected by UV absorbance at 210 nm. Serum concentrations (mean +/- s.e.m.) of epiroprim were highest at 30 min for both 50 and 100 mg kg-1 doses, 173 +/- 20 and 207 +/- 25 ng mL-1, respectively, falling to 8 +/- 5 and 18 +/- 6 ng mL-1, respectively, at 240 min. Epiroprim concentrations in the brain correlated well with those in the serum, with levels of 223 +/- 69 and 265 +/- 21 ng g-1 falling to 10 +/- 10 and 31 +/- 11 ng g-1, respectively. Epiroprim is rapidly absorbed and distributed to the brain.

Animals↗
PubMed1996

The potential role of azithromycin in the treatment of prophylaxis of toxoplasmosis.

Infection with Toxoplasma gondii is the most common parasitic infection worldwide with an estimated prevalence of 1-2 billion people. The risk of developing severe toxoplasmosis is higher for immunocompromised individuals and fetuses of mothers who have acquired a primo-infection. The current therapy of choice for toxoplasmosis is the synergistic combination of pyrimethamine and sulphadiazine. This therapy is highly effective but its use is complicated in immuno-compromised individuals due to adverse secondary effects. In addition, since pyrimethamine is potentially teratogenic, its use is not recommended during early pregnancy. Clindamycin, a lincosaminide, in combination with pyrimethamine has been shown to be an acceptable therapeutic alternative in patients who are unable to tolerate pyrimethamine plus sulphadiazine. In the search for new, effective compounds with less adverse or toxic effects, recent efforts have focused on the new macrolides and the azalides. Here, the results of the investigations and, in particular, the theoretical considerations for the potential use of azithromycin in the therapy of toxoplasmosis in immunocompromised individuals are reviewed.

AIDS-Related Opportunistic Infections↗
PubMed1996

Multicentric primary adenocarcinomas of the midgut: the first case report.

Multicentric adenocarcinomas of the midgut have not been described; even multiple adenocarcinomas limited to the small intestine are extremely uncommon, with only 14 cases reported in the literature. We report a case of multicentric synchronous involvement of the entire midgut with adenocarcinoma in a 52-yr-old Polish woman who had more than 30 lesions extending from duodenum to mid-transverse colon. There was no family history of cancer. Preoperative evaluation and intraoperative exploration were negative for primary malignancy of the lungs, breasts, ovaries, pancreas, and other parts of the gastrointestinal tract. Results of histopathological examination, immunohistochemical staining, and ras mutational analysis of the lesions uniformly support the diagnosis of multicentric poorly differentiated adenocarcinoma. The cause for this unusual presentation is unknown, although sporadic genetic alteration(s) of oncogene(s) might have been the precipitating event.

Adenocarcinoma↗
PubMed1995

Fish oil enhances macrophage tumor necrosis factor-alpha mRNA expression at the transcriptional level.

Dietary supplementation with fish oil has previously been shown to enhance in vivo and in vitro (macrophage) synthesis of tumor necrosis factor-alpha (TNF-alpha) in response to bacterial lipopolysaccharide (LPS) stimulation. The studies reported here were conducted to gain insight into the molecular mechanisms of this nutrient-immune interaction by comparing the concentration, rate of synthesis, and rate of decay of TNF-alpha mRNA upon LPS stimulation of macrophages obtained from mice fed high-fat diets, rich in either fish oil, corn oil, or coconut oil, or a low-fat diet for a period of 4 weeks. The results indicate that compared with the other diet groups, LPS stimulation of macrophages from mice fed fish oil resulted in (1) enhanced levels of mRNA and protein for TNF-alpha, and (2) increased transcription of TNF-alpha mRNA as assessed by nuclear run-on assays. Posttranscriptional studies showed that the rate of decay of TNF-alpha mRNA did not vary significantly for macrophages from mice fed with fish oil as compared with corn oil. Further studies using actinomycin D and cycloheximide suggested that RNA synthesis, but not protein synthesis, was necessary for TNF-alpha mRNA accumulation. Taken together, the present studies suggest that fish oil enhances macrophage TNF-alpha mRNA expression at the transcriptional level. Although such TNF-alpha upregulation may provide a mechanism for the beneficial effects of fish oil in certain inflammatory and immune disorders, it can also underlie its potential deleterious effects if the degree of upregulation leads to exaggerated TNF-alpha production that exceeds the limits of benefit to reach toxic levels.

Animals↗
PubMed1995

Comparison of multiplex PCR and culture for detection of Legionellae in cooling tower water samples.

We compared multiplex polymerase chain reaction (PCR) and culture for detecting the presence of Legionella pneumophila and Legionella spp in cooling tower water samples. Multiplex PCR was performed after phenol extraction of DNA from the samples. The set of primers for the PCR assay involved the 5S rRNA (Legionella spp) and the mip (macrophage infectivity potentiator gene, specific for L. pneumophila) genes as target sequences for amplification. Both the sensitivity and the specificity of the PCR assay were 100% when the 5S rRNA gene was used as target sequence. Isolation of Legionellae from the samples was observed only with the PCR-positive samples. We propose that PCR be used as a screening test before attempting to culture Legionellae from cooling tower water samples.

Air Conditioning↗
PubMed1994

Tumor-associated antigens recognized by human monoclonal antibodies.

BACKGROUND: Nonhuman monoclonal antibodies (MoAbs) of desired specificities have been studied in cancer treatment and tumor targeting with minimal success. Attempts of using humanized chimeric antibodies have not improved significantly their clinical applications. We have engaged in the development of human MoAbs by incorporating the in vitro immunization protocols to the nodal lymphocytes of cancer patients. Three human MoAbs thus generated were found to be strongly reactive with various human malignancies. The antigens recognized by the three antibodies were selected for immunochemical and biochemical characterizations. METHODS: The antigens investigated were AgSK1, PA 1-2 and PA 3-1. The patterns of each antigen expression in various human cancer cell lines were studied by the immunocytochemical staining technique. The expression of AgSK1 in association with cellular proliferation was examined by the flow cytometry analysis. In studying the biochemical natures of these antigens, their sensitivities toward various chemical and physical treatments were determined. The antigens that were shown to be proteins were subjected to SDS-PAGE and Western blot for estimations of molecular weights. RESULTS: The AgSK1 was detected in 10 human carcinoma cell lines but in none of the melanoma cell lines. This suggests that SK1 may be an epithelial or carcinoma marker. The phenotypic expressions of AgSK1 were shown to be associated with proliferation of carcinoma cells. Biochemically AgSK1 was a sialophycoprotein with an estimated molecular weight of 42-44 kilodaltons (kDa). HuMAb PA1-2 demonstrated a unique staining pattern at both the cytoplasmic and intercellular interface. The stained filamentlike structures extending from cell to cell indicated that Ag PA1-2 might play a role in cellular interactions. Biochemically, Ag PA1-2 appeared to be an asialocarbohydrate. The Ag PA3-1 was a cytoplasmic glycoprotein expressed by all 13 cell lines. The estimated molecular weights of PA3-1 were 164, 104, and 40 kDa. CONCLUSIONS: Tumor-associated antigens recognized by the human MoAbs may be more relevant clinically than those recognized by the mouse immune system. Carcinoma-specific human MoAbs are desirable for cancer treatment and tumor localization.

Antibodies, Monoclonal↗
PubMed1994

Cockayne syndrome in two adult siblings.

Although survival beyond the second decade is unusual in patients who have Cockayne syndrome, we describe two brothers with the syndrome who are 42 and 55 years of age. Their cultured skin fibroblasts showed extreme UV sensitivity but had almost normal UV-induced unscheduled DNA synthesis. The patients were classified as genetic complementation group B after study of the recovery of RNA synthesis after UV irradiation of fused cells. Clinical phototesting revealed a reduced threshold for UVB erythema.

Adult↗
PubMed1994

Antimicrobial susceptibilities of clinical isolates of Acinetobacter baumannii from Singapore.

The in vitro activities of 17 antimicrobial agents alone or in combination against 70 clinical isolates of Acinetobacter baumannii from Singapore were determined by broth microdilution. The MICs of amoxicillin, ampicillin, ceftazidime, ceftriaxone, gentamicin, and piperacillin for 90% of the strains were > or = 128 micrograms/ml. Addition of sulbactam to ampicillin produced improved activity, whereas adding tazobactam to piperacillin did not. The MICs of amikacin, ciprofloxacin, and imipenem for 90% of the strains were 32, 32, and 16 micrograms/ml, respectively.

Acinetobacter↗
PubMed1994

Activity of epiroprim (Ro 11-8958), a dihydrofolate reductase inhibitor, alone and in combination with dapsone against Toxoplasma gondii.

We examined the effect of epiroprim (Ro 11-8958), a dihydrofolate reductase inhibitor, alone and in combination with dapsone, against Toxoplasma gondii. In vitro, the anti-T. gondii effects of epiroprim and dapsone were observed at nanogram-per-milliliter levels when a 72-h uracil assay and an infection rate of one parasite per 120 macrophages were used. In combination, these drugs exerted a synergistic effect that, however, was only parasitostatic. In a model of acute infection, mice were infected intraperitoneally with 10(4) parasites of the RH strain of T. gondii and were treated for 14 days by gavage (therapy divided into two daily dosages), starting 24 h after infection. Used alone, dapsone and epiroprim, each at a dose of 50 mg/kg of body weight per day, protected 10 and 0% of the mice, respectively. When these drugs were administered simultaneously, a 100% survival rate was observed. Pyrimethamine-sulfadiazine (4 and 250 mg/kg/day, respectively) protected 100% of the mice. A 3-week therapy of chronically infected mice with either epiroprim (50 mg/kg/day), dapsone (50 mg/kg/day), or pyrimethamine (15 mg/kg/day) reduced the numbers of T. gondii cysts and the inflammation in their brains. A combination of epiroprim and dapsone, both at 50 mg/kg/day, further reduced the number of brain cysts in comparison with the number after the corresponding monotherapies. Epiroprim may have a role in the prophylaxis or therapy of human toxoplasmosis, especially when combined with other drugs active against T. gondii, such as dapsone.

Animals↗
PubMed1993

Expression and modulation of class I and class II histocompatibility leukocyte antigens on human soft tissue sarcomas.

BACKGROUND: Class I and Class II histocompatibility leukocyte antigens (HLA) play an important role in the antigenic recognition and target cell killing by T-lymphocytes. Their expression and modulation with gamma interferon on human soft tissue sarcomas were investigated. METHODS: The phenotypic expressions of Class I and Class II HLA were determined by avidin-biotin immunoperoxidase staining using two monoclonal antibodies W6/32 and MEL3, respectively. RESULTS: The present study showed that soft tissue sarcomas frequently had demonstrable Class I HLA and less-frequently expressed Class II HLA: The staining for Class I HLA was more diffuse, and the staining for Class II HLA was generally patchy in appearance. The expressions of two antigens on cultured sarcoma cells were found in accordance with the findings of sarcoma tumors. The expression of Class I antigen was enhanced, and Class II was induced in two cell lines by gamma interferon. The in vitro modulation of HLA with gamma interferon was reversible. Gamma interferon at the testing dose did not have cytotoxic or antiproliferative effects on either cell lines. CONCLUSIONS: Through the modulation of HLA on soft tissue sarcomas, gamma interferon may play a role in the clinical management of sarcomas.

Cell Division↗
PubMed1993

AgSK1, a novel carcinoma associated antigen.

An IgM human monoclonal antibody (HuMAb) SK1 was generated from mesenteric nodal lymphocytes of a colon cancer patient that were fused with a human B-lymphoblastoid cell line SHFP-1. The reactivities of HuMAb SK1 to various human cell lines were screened by cell enzyme linked immunosorbent assay and immunocytochemical staining. The HuMAb SK1 reacted strongly with all 11 human carcinoma cell lines that were tested and had no detectable binding with noncarcinoma cell lines of the following origins: fibroblast; fetal lung; melanoma; soft tissue sarcoma; neuroblastoma; and glioblastoma. Carcinoma preferred reactivity of HuMAb SK1 was further confirmed by immunoperoxidase staining of a large number of frozen tissues, both malignant and benign. The antigen SK1 (AgSK1) in human carcinoma detected by immunoperoxidase staining was also identified biochemically as a sialoglycoprotein that migrated at M(r) 42,000 with an isoelectric point (pI) of approximately 5.9. A preferential staining by HuMAb SK1 was seen among colorectal, gastric, pancreatic, and lung cancers. Competitive inhibition study in solid-phase immunoassay suggested that the HuMAb SK1 did not cross-react with other antibodies specific for CEA, CA 19-9, and TAG 72. The AgSK1 appears to be a novel carcinoma associated antigen which may be a useful tumor marker in cancer diagnosis and treatment.

Animals↗
PubMed1993

Respective role of polymorphonuclear leukocytes and their integrins (CD-11/18) in the local or systemic toxicity of lipopolysaccharide.

The role of neutrophils (PMNs) and leukocyte integrins was investigated in two models of lipopolysaccharide (LPS)-induced toxicity: the systemic lethality assay in D-galactosamine-sensitized mice and the local reaction elicited by intradermal injection of LPS and tumor necrosis factor (TNF) at 24-h intervals. In the local reaction, depletion of PMNs with an anti-PMN monoclonal antibody (mAb) and mAbs against CD-11a (or LFA1) and CD-11b (or CR3) completely prevented the hemorrhagic necrosis. Evaluation of histological sections and myeloperoxidase levels suggested different mechanism of protection because PMNs were abundant in anti-CD-11- and absent in anti-PMN-treated mice. In the systemic assay, depletion of PMNs ensured 100% survival, whereas after administration of anti-CD-11a or b mAb, the percentages of survivors were 6 and 59%, respectively. One hour after LPS injection, the serum TNF-alpha level was higher in PMN-depleted mice than in controls. These studies provide evidence that neutrophils are essential for the expression of local or systemic LPS-induced injury, whereas the requirement for their leukocytic integrins is obvious only in the local reaction.

Animals↗