Search PubMed⌕ Search

Biomedical subjects

J Chang

Publications and source records attributed to J Chang.

At least 343 records · Page 19Linked to original sources
PubMed1995

Role of protein kinase C subtypes alpha and delta in the regulation of bradykinin-stimulated phosphoinositide breakdown in astrocytes.

Cultured astrocytes express bradykinin (BK) receptors coupled to phospholipase C (PLC)-mediated phosphoinositide (PI) hydrolysis. Short term (10- or 90-min) treatment of cells with 1 microM 12-O-tetradecanoylphorbol-13-acetate (TPA) decreased BK-induced PI breakdown, but this inhibitory action was lost after 3-hr TPA treatment. Extended (6- or 24-hr) pretreatment resulted in marked potentiation of the BK response. Western blot analysis using protein kinase C (PKC) isozyme-specific antibodies indicated that astrocytes express PKC-alpha, PKC-delta, and PKC-zeta. With TPA treatment of the cells for various times (10 min, 90 min, 3 hr, 6 hr, or 24 hr), translocation of PKC-alpha and PKC-delta from the cytosol to the membrane was seen after 10- or 90-min treatment and restoration to basal levels in the membrane fraction was seen after 3-hr treatment. However, partial or complete down-regulation of PKC-alpha and PKC-delta was seen after 6- or 24-hr treatment, respectively. No translocation or down-regulation of PKC-zeta was seen after either short term or long term TPA treatment. The inactive phorbol ester alpha-TPA had no effect on BK-induced PI hydrolysis or on the translocation or down-regulation of PKC-alpha and PKC-delta. These results suggest that, in unstimulated astrocytes, both PKC-alpha and PKC-delta, but not PKC-zeta, may exert tonic inhibition of BK-mediated PI turnover. After 10- or 90-min TPA treatment, AIF4(-)--but not Ca2+ ionophore-induced PI hydrolysis was inhibited, whereas [3H]BK binding was unaffected, indicating that the site of action of PKC-alpha and PKC-delta in the BK receptor/G protein/PLC pathway is after the receptor and before PLC, i.e., the G protein. After down-regulation of PKC-alpha and -delta, increases in both AIF4(-)-induced inositol phosphate formation and [3H]BK binding contributed to marked potentiation of BK-induced PI responses. Scatchard plot analysis showed an increase in both the maximal number of binding sites and the binding affinity. Both the up-regulation of [3H]BK binding and the subsequent BK-induced PI turnover were blocked by 0.5 microM cycloheximide, a protein synthesis inhibitor. The increase in AIF4(-)-induced PI hydrolysis after 24-hr TPA treatment was also inhibited by cycloheximide, indicating that new synthesis of BK receptors and G proteins was required after down-regulation of PKC-alpha and PKC-delta.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

[Investigation of the relationship between white lesion of vulva and human epidermal growth factor].

The levels of human epidermal growth factor (hEGF) were determined by radioimmunoassay (RIA) in dermal specimens taken from lesion skin and normal vulva skin in 30 patients with white lesions of the vulva as well as their urine specimens, and in another 29 vulva biopsy and 37 urine samples from healthy women without the disease as the control group. The results showed that the mean hEGF levels in lesion vulva skin, normal vulva skin of the patients and normal vulva skin of healthy women were 163.40 +/- 97.89 micrograms/L, 119.00 +/- 53.13 micrograms/L and 67.84 +/- 14.72 micrograms/L respectively. The level of hEGF in lesion skin was higher than that in the normal vulva skin of same patients (P < 0.05) and also higher than that in the normal skin of healthy women (P < 0.01). The hEGF level in normal skin of the patients was higher than that in healthy women (P < 0.01). The hEGF level in lesion skin had no relationship with pathological types. The hEGF levels in urine had no significant difference between the patients and healthy women. The results suggested that high levels of hEGF in local vulva lesions may play an important role in the pathogenesis of white lesions of the vulva.

Adult↗
PubMed1995

In vivo and in vitro studies of Clostridium difficile-induced disease in hamsters fed an atherogenic, high-fat diet.

After previous observation of increased susceptibility to Clostridium difficile enterocolitis in hamsters fed an atherogenic, high-fat diet, a study was undertaken to examine experimental reproducibility of this disease. Hamsters were fed either the high-fat diet or a control diet, then orally challenged with a toxigenic strain of C. difficile. Hamsters fed the high-fat diet suffered 80% morbidity, which was statistically significant from the 11% morbidity of the control diet group (P < or = 0.05). The disease presented acutely, the most common presentation being sudden death. The most common lesions in the affected hamsters were necrohemorrhagic cecitis and cecal mucosal hyperplasia. Hepatic lipidosis was consistent in all hamsters fed the high-fat diet. Toxigenic C. difficile could be recovered from the cecum of most affected hamsters, and toxins A and B were detected in these ceca. Hamsters that were fed the high-fat diet and orally inoculated with a nontoxigenic strain of C. difficile before experimental challenge with a toxigenic strain were initially protected against disease. The protection decreased with each exposure to the toxigenic strain. Results of in vitro colonization-resistance studies indicated that the cecal flora from hamsters fed the high-fat diet and control diets inhibited C. difficile growth, suggesting that increased disease susceptibility was not the result of altered cecal flora.

Animals↗
PubMed1995

Experimental renal artery stenosis and angioplasty. The mechanism of the angioplasty.

The mechanism of percutaneous transluminal renal angioplasty (PTRA) was studied in 18 dogs. The dogs were divided into two groups. Seven dogs were in the early group and eleven were within 1-3 weeks after PTRA. A 4/0 resorbable chronic catgut was used to ligate subtotally the renal artery to create fibromuscular dysplasia. PTRA was performed after renal artery stenosis for 6-8 weeks. The changes of ultrastructure of renal artery were studied. A contrary orientation balance hypothesis was proposed to explain the mechanism of PTRA.

Angioplasty, Balloon↗
PubMed1995

[A research on serum, urine and tumor tissue hyaluronate assays for detecting malignant ovarian tumors].

Hyaluronate contents were determined by radioimmunoassay in 91 samples of serum, 88 samples of urine and 32 samples of ovarian tumor tissue from patients with benign and malignant tumors and from healthy subjects. The mean serum hyaluronate level in patients with malignant ovarian tumors (mean, 155.99 micrograms/L, range, 20 to 680 micrograms/L) was significantly higher than that in patients with benign ovarian tumors (mean, 84.2 micrograms/L; range, 20 to 188 micrograms/L) and that in healthy subjects (mean, 57 micrograms/L; range, 2 to 110 micrograms/L). The mean urine hyaluronate level in the malignant group (mean, 307.83 micrograms/L; range 50 to 750 micrograms/L) also was significantly higher than that in the normal control group (mean, 146 micrograms/L; range, 40 to 242 micrograms/L). The results suggest that serum and urine hyaluronate determination in the detection of malignant ovarian tumors is of clinical value.

Adult↗
PubMed1995

[Characteristics and recent trends in endemicity of human parasitic diseases in China].

An analysis of the nationwide survey of the distribution of human parasites in the light of the literature previously published, two major trends in the endemicity of parasitic diseases in China was observed. For one trend, the infection rate of E. histolytica, Fasciolopsis buski and soil-transmitted helminthasis etc. declined markedly. The second trend was that the prevalence of food-transmitted parasitic diseases (Trichinella spiralis, Clonorchis sinensis, Paragonimiasis, cysticercosis) and hydatidosis was increasing. The relationship between the social economic factors and the two trends were discussed.

Animals↗
PubMed1995

Four outbreaks of human trichinellosis in Henan Province.

Four outbreaks of human trichinellosis caused by eating pork together had occurred successively in two rural areas and two cities of Henan Province, where the disease is endemic. Of the 110 persons involved, 54 had the onset. All of them had the history of eating pork. In the outbreak of Dengzhou, in those persons who dined together, men were all uninfected and 13 women were infected. The difference found between sexes was suggested to be related with spirit drinking. In these 54 patients, the latent period ranged from 3 to 28 days. The relevant clinical symptoms and signs were fever, edema, myalgia, rash, headache, nausea, abdominal pain and diarrhea. Vomiting was uncommon. Most patients were hospitalized and all cases recovered in two weeks after proper treatment with albendazole.

Animals↗
PubMed1995

[Relationship between the structure--modified N- and C- termini and the biological activity of TNF alpha molecule].

In order to elucidate the relationship between N-, C-termini of TNF alpha and it's biological activity, a TNF alpha derivative 10 (TNF alpha D10) was prepared by changing amino acid at the N-terminus positions Ser(4), Ser(5), Asp(10) and C-terminus position Leu(157) to N-terminus Cys(4), Thr(5), Arg(10) and C-terminus Phe(157) with PCR site-directed mutagenesis. The results showed that the expression level of this mutein has not altered but its cytotoxic activity increased. This might result from trimer formation of TNF alpha D10 by changing N-terminal Ser(4) residue to Cys. HPLC showed that the molecular weight of TNF alpha D10 was 17kD, 35kD, 55kD respectively. In addition, we also found that the stability of TNF alpha D10 was less than that of TNF alpha when to be stored at -20 degrees C for two months. It might be caused by changing Leu(157) to Phe(157).

Base Sequence↗
PubMed1995

Effect of 3'-untranslated region on expression of TNF alpha cDNA in Escherichia coli.

A construct pRL-rhTNF alpha 2, in which the 110 bp 3'-untranslated region of rhTNF alpha cDNA was deleted, was transformed in E.coli. The expression level of several positive transformants was determined. The results showed that the expression of pRL-TNF alpha 2 was stable and the biological characteristics of the protein product were the same as that of pRL-rhTNF alpha. Furthermore, the expression level of pRL-rhTNF alpha 2 was increased. It is suggested that the 3'-untranslated region may have some effects on gene expression. A TA-rich sequence, TTTATTA, contained in the 3'-untranslated region of pRL-rhTNF alpha may be involved in the inhibitory effect on gene expression.

Base Sequence↗
PubMed1994

Residential radon exposure and lung cancer among nonsmoking women.

BACKGROUND: Radon at sufficiently high concentrations is known to cause lung cancer among underground miners and in experimental laboratory animals. PURPOSE: Our aim was to determine whether indoor levels of radon are associated with a detectable increase in lung cancer. Nonsmoking women were selected because they offer the best opportunity to detect radon-related risk while minimizing the potentially confounding influences of cigarette smoking and occupation. METHODS: A population-based, case-control study of incident lung cancer was conducted in Missouri. A total of 538 non-smoking white women diagnosed with lung cancer between 1986 and 1992 and 1183 age-matched control subjects were identified from the Missouri Cancer Registry and from driver's license and Medicare listings, respectively. Information on lung cancer risk factors was obtained by telephone interview. Year-long radon measurements were sought in every dwelling occupied for the previous 5-30 years. RESULTS: Radon measurements covered 78% of the relevant residential period, and women reported being indoors for 84% of this time. The time-weighted average radon concentrations were exactly the same for case subjects and control subjects (1.82 pCi/L of air [pCi L-1]). Radon levels greater than 4 pCi L-1 were experienced by 6.5% of the case subjects and 6.8% of the control subjects. For all data combined, there was little evidence for a trend of lung cancer with increasing radon concentrations (two-tailed trend test, P = .99 continuous data analysis; P = .19 categorical data analysis). A positive dose-response trend was suggested for the adenocarcinoma cell type and among directly interviewed women (two-tailed trend test; P = .31 continuous data analysis; P = .04 categorical data analysis), but not for other histologies or among those who had surrogate interviews. CONCLUSIONS: The possibility of detecting a risk from indoor radon in this study was maximized by (a) including a large number of nonsmoking women with high indoor occupancy, (b) conducting a large number of radon measurements near the time of the diagnosis of cancer, and (c) controlling for known causes of lung cancer. However, an association between lung cancer and the exposure to domestic levels of radon was not convincingly demonstrated. IMPLICATIONS: The magnitude of the lung cancer risk from radon levels commonly found in U.S. dwellings appears low.

Adenocarcinoma↗
PubMed1994

Carcinomatous meningitis in patients with breast cancer. An aggressive disease variant.

BACKGROUND: Carcinomatous meningitis is a rare and often devastating complication in patients with breast cancer, and the treatment is controversial. METHODS: A retrospective analysis of 35 patients with carcinomatous meningitis from breast cancer was performed to define the biology of the disease and to guide treatment. RESULTS: An aggressive variant of breast cancer was revealed: meningeal metastasis complicates less than 3.5% of cases of metastatic breast carcinoma. Sixty-seven percent of these patients had tumors that were lobular or combined lobular/ductal histology; the median intervals from primary treatment to disease recurrence and from recurrence to death were 10.9 and 15 months, respectively. The median survival after diagnosis of carcinomatous meningitis was 77 days. The most significant prognostic factor was the Karnofsky performance status (KP) at presentation of meningeal disease. Patients with a KP greater or equal to 70 survived a median of 313 days, whereas those with a KP of 60 or less survived for a median of 36 days (P = 0.0002). In addition, there was a trend suggesting that the response 2 weeks after treatment was initiated, correlated with survival. CONCLUSIONS: Carcinomatous meningitis from breast carcinoma is an aggressive metastatic complication with a poor prognosis. The authors suggest that patients with a poor KP (< 70) should be treated symptomatically and those with a good KP (> or = 70) should receive more aggressive treatment. The patients' survival in this study compared well with other reports, and yet, only one patient was treated with intraventricular chemotherapy. Therefore, these data question the superiority of intraventricular treatment versus other modalities.

Adult↗
PubMed1994

Haemopoietic progenitor and myeloid cell kinetics in humans treated with interleukin-3 and granulocyte/macrophage colony-stimulating factor in combination.

Patients with advanced adenocarcinoma of the colon, rectum or pancreas were entered into trials for evaluation of treatment with sequential doses of IL-3 and GM-CSF. They received 0.25 to 5 micrograms IL-3/kg/d for up to 7 days, followed by 1 microgram GM-CSF/kg/day for a maximum of 10 further days. We assessed the kinetics of bone-marrow cell proliferation and of blood production using tritiated thymidine labelling in vitro and in vivo. Megakaryocytic-CFC were unaffected but proliferation rates of GM-CFC and BFU-E were increased. Progenitor cells were mobilized (12-fold over baseline) into the peripheral blood. The proliferative activity of maturing cells in the marrow was increased (cell-cycle times were reduced by at least 30%). This translated into amplified blood cell production (WCC approximately 30 x 10(9)/l), a 2.2-fold increase in platelet counts and significant eosinophilia. Newly generated neutrophils appeared in the circulation at the normal time and their peripheral half-life was also normal. The calculated 3.2-fold amplification in neutrophil production required nearly 2 extra divisions in the marrow, shared between the progenitors and the proliferating granulocytic cells. The results were compared with those of a previous trial using GM-CSF only, although at a 10-fold higher dose level. Comparable levels of peripheral neutrophils were obtained in both trials but significant ineffective granulopoiesis developed in the earlier study. This was overcome in the present study, the priming dose of IL-3 apparently giving the latitude to utilize lower doses of GM-CSF with less risk of complications.

Adenocarcinoma↗
PubMed1994

Altered angiogenesis underlying age-dependent changes in tumor growth.

BACKGROUND: Cancer incidence increases with age, but the growth and spread of tumors is often slow and prolonged in the elderly. Transplantable murine tumors grow and spread less readily in older mice and can be used as models to study the effect of host age. Neovascularization is crucial for the growth of solid tumors, and alterations in the host vascular response may underlie the changes in tumor growth occurring with age. PURPOSE: We have used transplantable tumor cells and tumors, and tumor extracts, to better understand differences in the biology of tumor growth and vascularization as a function of host age. METHODS: Englebreth-Holm-Swarm (EHS) carcinoma and B16-F10 melanoma cells were injected into C57BL mice of different ages. Tumor growth, histology, and cellular DNA synthesis were compared. Vascularization was determined using basic fibroblast growth factor and an in vivo angiogenesis assay. EHS tumor extracts were assayed for biologic activity in vitro using human endothelial cells and in vivo using mouse EHS-BAM carcinoma and human TSU-Pr1 prostate carcinoma cells. RESULTS: EHS tumors formed larger tumors in young than in old C57BL mice. Rapid tumor growth resumed upon transfer of tumor tissue from old animals into young animals. The rate of DNA synthesis of tumor tissue from old animals in organ culture was lower than in tissue from young animals. Histologically, tumors grown in old animals exhibited a threefold higher ratio of extracellular matrix to tumor cells than those grown in young animals. Tumors from adult animals exhibited numerous small blood vessels; those from old animals contained fewer, much larger vessels. Similar results were observed in young mice fed a reduced-calorie diet. Young animals elicited a greater and more rapid angiogenic response than old animals. Extracts of tumors grown in old animals failed to support endothelial cell differentiation in culture. Tumor cells injected together with such old extracts showed reduced tumor growth in nude mice. CONCLUSIONS: The rate of growth and morphology of the EHS tumor were altered with age, partly due to a reduced capacity to vascularize the tumors because of a lack of angiogenic factors or the presence of host inhibitors. IMPLICATIONS: Alterations in host factors detected in this tumor model may underlie a variety of age-dependent changes that could influence tumor growth and the repair and regeneration of normal tissue. Reducing the vascularization of tumors represents a potential target to reduce their growth and progression.

Aging↗
PubMed1994

Role of the intestinal microbiota in the activation of the promutagen 2,6-dinitrotoluene to mutagenic urine metabolites and comparison of GI enzyme activities in germ-free and conventionalized male Fischer 344 rats.

After male germ-free and conventionalized Fischer 344 rats were administered per os (p.o.) 75 mg/kg 2,6-DNT, intestinal nitroreductase, beta-glucuronidase, and azo reductase activities were lower in the cecum and large intestine of germ-free animals. However, there was no significant difference in the small intestinal nitroreductase and azo reductase compared to the conventionalized counterparts. This indicated a potential mucosal source for the enzymes. Urines from germ-free rats (1144 +/- 64 revertants/ml) were less mutagenic than those from conventionalized animals (1467 +/- 171 revertants/ml) in Salmonella typhimurium strain TA98 without S9. In the presence of S9, urine from conventionalized animals (894 +/- 56 revertants/ml) was more mutagenic than that from germ-free rats (686 +/- 60 revertants/ml). The presence of the intestinal flora plays an important role in the activation of 2,6-DNT but other metabolic pathways, such as the small intestinal mucosal and/or hepatic enzymes, are present that can generate excreted genotoxicants.

Animals↗
PubMed1994

Activation of beta 1 integrin fibronectin receptors on HL60 cells after granulocytic differentiation.

Phorbol esters upregulate the functional affinity of beta 1 integrin receptors for fibronectin on human neutrophils and other leukocytes. We investigated the ability of phorbol myristate acetate (PMA) to stimulate the human promyelocytic cell line HL-60 to adhere to fibronectin, either in its undifferentiated state (HL60) or after dimethylsulfoxide-induced differentiation along the granulocytic pathway (dHL60). PMA stimulated little adherence of undifferentiated HL60 to fibronectin or to the 120-kD chymotryptic cell-binding domain (CBD) of fibronectin. In contrast, PMA stimulated dHL60 cells to rapidly adhere to both fibronectin- and to CBD-coated plastic. PMA-stimulated dHL60 adherence to fibronectin was largely mediated by both alpha 4 beta 1 and alpha 5 beta 1, whereas PMA-stimulated dHL60 adherence to CBD was largely mediated by alpha 5 beta 1. There was little contribution from beta 2 integrins to PMA-stimulated dHL60 adherence to fibronectin or CBD. The inability of undifferentiated HL60 to adhere to fibronectin and CBD did not result from lack of expression of alpha 4 beta 1 or alpha 5 beta 1 because HL60 and dHL60 express similar amounts of both alpha 4 beta 1 and alpha 5 beta 1 on their surface. In addition, 1 mmol/L Mn2+ induced similar amounts of alpha 5 beta 1-dependent adherence of both HL60 and dHL60, showing that alpha 5 beta 1 on undifferentiated HL60 is capable of binding to its ligand. These data suggest that activation of protein kinase C cannot functionally upregulate these beta 1 integrins on undifferentiated HL60 cells. The development of PMA-stimulated beta 1-dependent adherence after granulocytic differentiation of HL60 cells suggests that the differentiated HL60 cell is a useful model for investigating functional coupling of protein kinase C to beta 1 integrin in myeloid cells.

Animals↗
PubMed1994

The magnitude of HIV replication in monocytes and macrophages is influenced by environmental conditions, viral strain, and host cells.

It has been difficult to standardize the effects of various stimuli on HIV replication in monocytes and macrophages in different laboratories. In this study we have shown that it is possible to standardize HIV inocula, culture conditions, and HIV antigen assay to achieve reproducibility with the same viral isolate and donor monocyte and macrophage. However, changes in serum concentration, in the strain of blood-derived isolate (even at low passage), in the donor source of the monocyte/macrophage, and in the state of cellular maturation all influenced HIV production by these cells. The donor source of monocytes contributed as much to variability in HIV production as the HIV strain and results were reproducible when the same source was used repeatedly. These in vitro data suggest that genetic differences may contribute to differences in HIV replication in macrophages and consequently to tissue virus load in vivo.

Antigens, Viral↗