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Biomedical subjects

J Chang

Publications and source records attributed to J Chang.

At least 361 records · Page 20Linked to original sources
PubMed1994

HIV infection of placental macrophages: their potential role in vertical transmission.

Placental macrophages were isolated and cultured in vitro to investigate their susceptibility to HIV infection and possible role in vertical transmission of HIV. After 10 days of in vitro culture the cells were positive for nonspecific esterase and acid phosphatase and negative for myeloperoxidase and placental alkaline phosphatase. They expressed cell surface HLA-ABC, HLA-DR, CD45, as well as CD68 intracellularly, as detected by flow cytometry, confirming their macrophage lineage. Approximately 80% of cells expressed surface CD14. CD4 antigen was expressed at very low levels and was confirmed by antibody blocking experiments. Infection of placental macrophage cultures with HIV resulted in a transient peak of viral replication 3 to 7 days after infection, but no later rise in HIV was detected with culture of up to 60 days. HIV replication was not up-regulated by coculture with phytohemagglutinin-stimulated lymphocytes or by treating infected cultures with tumor necrosis factor alpha or granulocyte-macrophage colony-stimulating factor.

Acid Phosphatase↗
PubMed1994

Molecular mechanisms of IL-4 effect on HIV expression in promonocytic cell lines and primary human monocytes.

HIV-1 can productively infect mononuclear phagocytes derived from blood, bone marrow, brain, and lung. Interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha) have previously been shown to stimulate HIV replication in monocytes and macrophages. The mechanism of IL-4 stimulation was investigated and compared with the known effects of TNF-alpha. IL-4 up-regulated the expression of HIV mRNA within the first 2 days after infection of promonocytic U-937 cells and 3 to 4 days after infection of plastic-adherent blood macrophages with HIV-1. TNF-alpha also up-regulated production of HIV RNA but to a greater degree than IL-4, reaching a peak 3-4 days after addition. Northern blot analyses showed an increase in genomic and spliced RNAs at these times. However, there was reduced stimulation of HIV mRNA production when IL-4 and TNF-alpha were combined. These techniques are being used to further elucidate the mechanism of action of cytokines that inhibit HIV replication in purified human monocytes and macrophages.

Blotting, Northern↗
PubMed1994

Effect of Ni(II) on tissue hydrogen peroxide content in mice as inferred from glutathione and glutathione disulfide measurements.

Studies on Ni(II)-induced carcinogenesis have suggested that oxidative damage caused by Ni(II) may in part be due to increased tissue H2O2 formation. However, there is lack of evidence in vivo. Because of limitations of available methods for direct measurement of the in vivo rate of H2O2 formation in animals, Ni(II)-induced production of H2O2 was estimated from changes in the rate of glutathione disulfide (GSSG) formation. Male B6C3F1 mice (6-8 wk old) were injected i.p. with 170 mumol NiAc2/kg. Biliary efflux and liver, kidney, and lung levels of glutathione (GSH and GSSG) were determined 0-2 h after treatment. In spite of slight increases in tissue GSSG levels by Ni(II), there was no significant change in the biliary efflux of GSSG. Pretreatment with 50 mg/kg (i.p.) of bis-chloroethyl-nitrosourea (BCNU), an inhibitor of GSSG reductase, did not augment the effects of Ni(II) on GSSG formation significantly. Based on these observations, it was apparent that Ni(II) did not change the concentration of H2O2 significantly in vivo.

Animals↗
PubMed1994

A phase II study of the sequential administration of dacarbazine and fotemustine in the treatment of cerebral metastases from malignant melanoma.

34 patients with cerebral metastases from malignant melanoma received sequential dacarbazine at 250 mg/m2 followed 2 h later by fotemustine at 100 mg/m2; this was repeated on day 8. Maintenance therapy was given every 4 weeks to patients with radiological evidence of response or stable disease until a maximum response was achieved plus two more cycles. A 12% response rate was obtained for cerebral metastases, with 2 complete responses lasting 12 and 36+ months, and 2 partial responses lasting 2.5 and 3.75 months. Toxicity was mainly haematological with grade 3-4 leucopenia and thrombocytopenia in 23.5% of patients. No pulmonary toxicity was seen. This schedule of sequential dacarbazine and fotemustine has low activity against metastatic melanoma, and the response rate for cerebral metastases is not superior to that shown in other studies with single agent fotemustine, but the treatment was well tolerated and can be delivered on an outpatient basis.

Adult↗
PubMed1994

Identification, developmental expression and tissue distribution of deaminoneuraminate hydrolase (KDNase) activity in rainbow trout.

A deaminoneuraminosyl-glycohydrolase (KDNase), which catalyses the hydrolysis of alpha-ketosidic 2-keto-3-deoxy-D-glycero-D-galacto- nononic acid (or naturally occurring deaminated neuraminic acid; KDN) linkages in KDN-glycoconjugates, is required for their structural and functional studies since KDN residues are usually resistant to the action of known sialidases. A search for KDNase was initiated by examining various cells and tissues of rainbow trout because KDN-glycoconjugates were first found in this animal species. Tissue localization studies of KDNase activity showed it to be present in kidney, spleen and ovary. The highest KDNase activity was found in ovarian post-ovulatory follicles obtained from female fish at the time when the reproductive organ was undergoing natural effacement. Little if any activity was found in brain, heart, liver, muscle, mature eggs and testis. Developmentally, higher levels of KDNase were usually expressed 3-4 months before ovulation or spermiation. An exception to this was in the ovary (or ovarian follicles) where the most striking increase in KDNase occurred 1-2 months after the maturation of gamete cells. Enzyme extracts containing KDNase activity also contained sialidase activity. From the data based on a kinetic study using mixed substrates, both KDNase and sialidase activities were indicated to reside on a single enzyme protein. The KDN-sialidase displayed broad specificity, which could possibly limit its usefulness as a probe for KDN-glycoconjugates. Nevertheless, unlike sialidases, KDNase can selectively remove KDN residues, thus making it an important new reagent to identify KDN-glycoconjugates in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Interleukin 4 and human immunodeficiency virus stimulate LFA-1-ICAM-1-mediated aggregation of monocytes and subsequent giant cell formation.

The effects of recombinant interleukin 4 (IL-4) on cell cluster and multinucleated giant cell (MGC) formation from human immunodeficiency virus (HIV)-infected and uninfected monocytes were examined. Human blood monocytes were isolated by centrifugal elutriation and monoclonal antibody-complement-dependent lysis of residual T cells, and infected with low passage HIV strains. Monocytes were exposed to recombinant IL-4 (1 to 20 ng/ml), continuously after inoculation with HIV. Monocyte expression of ICAM-1 but not LFA-1 was significantly enhanced by IL-4 although substrate adherence was a more potent stimulus. Monocyte cluster and MGC formation was quantified after fixation and staining with Giemsa. Clusters of HIV-infected and uninfected monocytes were consistently and significantly increased at 4 to 7 days after IL-4 stimulation. The combination of HIV and IL-4 was more stimulatory than either treatment alone. In two out of five uninfected and three out of seven HIV-infected monocyte cultures, MGC formation was also markedly increased at 10 to 14 days after stimulation. Incubation with anti-LFA-1 (anti-CD11a, anti-CD18) and anti-ICAM-1 (anti-CD54) monoclonal antibodies reduced IL-4-stimulated aggregation in HIV-infected and uninfected monocytes and subsequently reduced MGC formation. Anti-ICAM-1 was not as effective as anti-CD11a or anti-CD18 in inhibiting aggregation of HIV-infected monocytes and in these cultures anti-ICAM-2 was also inhibitory. Extracellular HIV antigen concentrations were not consistently reduced by anti-CD11a or anti-ICAM-1. Hence IL-4 markedly enhanced monocyte aggregation in both HIV-infected and uninfected monocytes, probably through enhanced LFA-1-ICAM-1 interactions in all cultures and LFA-1-ICAM-2 interactions in infected monocytes, leading subsequently to MGC formation in some cultures.

Antibodies, Monoclonal↗
PubMed1994

Microbial succession and intestinal enzyme activities in the developing rat.

The succession of gut bacteria and selected intestinal enzyme activities in developing 7-35-d-old rats was studied. Aerobes and anaerobes were identified as members of four broad major bacterial groups, i.e. Gram-positive rods, Gram-positive cocci, Gram-negative rods and obligate anaerobes. The enzyme activities of nitro and azo reductases, beta-glucuronidase, dechlorinase and dehydrochlorinase were determined by anaerobic incubation of intestinal homogenates with 3,4-dichloronitrobenzene, methyl orange, p-nitrophenyl-beta-D-glucuronide, and p,p'-DDT respectively. Nitroreductase and azo reductase activities increased significantly with the appearance of anaerobes in the large intestine. No increase in either nitroreductase or azo reductase activities in the small intestine was found. The early and high level of beta-glucuronidase activity in the small and large intestines coincided with high numbers of coliforms recovered in 7 and 14 d animals. Dehydrochlorinase activity appeared early but was undetectable at both 21 and 28 d. Its activity increased at 35 d. Dechlorinase activity was variable in development. The rapid changes in the microbial flora and intestinal enzyme activities may influence the susceptibility of pre-pubescent rats to a variety of toxicants. Therefore, age-dependent toxicity may be important in the risk assessment of some environmental chemicals.

Age Factors↗
PubMed1994

Aminophylline therapy and cerebral blood flow velocity in preterm infants.

Pulsed Doppler ultrasound was used to evaluate the cerebral blood flow velocity (CBFV), in the middle and anterior cerebral arteries in 10 infants before and after the administration of aminophylline (7.5 mg/kg). Mean CBFV, heart rate, blood pressure, oxygen and carbon dioxide tensions were recorded before the loading dose, and then at 1, 2, 6 and 24 h after completion of the infusion. Mean CBFV in the middle and anterior cerebral arteries were 16.8 cm/s and 10.8 cm/s respectively prior to the infusion. There was a significant decrease (P < 0.05) in velocities in both arteries at 1 and 2h post drug therapy, which returned to base values by 6 h, and remained as such at 24 h. The heart rate increased (P < 0.05) after the infusion, while no consistent changes were observed in blood pressure or oxygen tension. Carbon dioxide levels were significantly reduced (P < 0.05) at 2 h. The reduction in CBFV, however, was more than would be expected on the basis of the change in carbon dioxide levels alone, suggesting that other factors may be exerting an influence. While no adverse effects were noted in the infants studied, it is suggested that aminophylline should be used judiciously in sick preterm infants at highest risk from ischaemic brain injury.

Aminophylline↗
PubMed1994

The Bel1 protein of human foamy virus contains one positive and two negative control regions which regulate a distinct activation domain of 30 amino acids.

The Bel1 transactivator is essential for the replication of human foamy virus (HFV). To define the functional domains of HFV Bel1, we generated random missense mutations throughout the entire coding sequence of Bel1. Functional analyses of 24 missense mutations have revealed the presence of at least two functional domains in Bel1. One domain corresponds to a basic amino acid-rich motif which acts as a bipartite nuclear targeting sequence. A second, central domain corresponds to a presumed effector region which, when mutated, leads to dominant-negative mutants and/or lacks transactivating ability. In addition, deletion analyses and domain-swapping experiments further showed that Bel1 protein contains a strong carboxy-terminal activation domain. The activating region is also capable of functioning as a transcription-activating domain in yeast cells, although it does not bear any significant sequence homology to the well-characterized acidic activation domain which is known to function only in yeast and mammalian cells. We also demonstrated that the regions of Bel1 from residues 1 to 76 and from residues 153 to 225 repressed transcriptional activation exerted by the Bel1 activation domain. In contrast, the region from residues 82 to 150 appears to overcome an inhibitory effect. These results indicate that Bel1 contains one positive and two negative regulatory domains that modulate a distinct activation domain of Bel1. These regulatory domains of Bel1 cannot affect the function of the VP16 activation domain, suggesting that these domains specifically regulate the activation domain of Bel1. Furthermore, in vivo competition experiments showed that the positive regulatory domain acts in trans. Thus, our results demonstrate that Bel1-mediated transactivation appears to undergo a complex regulatory pathway which provides a novel mode of regulation for a transcriptional activation domain.

Amino Acid Sequence↗
PubMed1994

[Report on the first nationwide survey of the distribution of human parasites in China. 1. Regional distribution of parasite species].

A nationwide (Taiwan Province not included) survey of the distribution of human parasites in China during 1988-1992 was conducted under the auspices of the Ministry of Public Health, with stratified masses randomly sampling. A total of 2,848 pilot sites in 726 counties with a population of 1,477,742 were surveyed, according to unified standard, unified diagnostic method and control quality. The overall infection rate of parasites was 62. 632%. Among them, the infection rate was over 50% in 17 provinces/autonomous regions/municipalities (P/A/M), over 80% in Hainan, Guangxi, Sichuan, Fujian, Zhejiang and Guizhou, being highest in Hainan (94. 735%). Altogether 56 species were detected. Centrocestus formosanus is reported for the first time at home, Echinochasmus liliputanus and Echinostoma angustitestis are reported for the first time at home and abroad. Echinochasmus fujianensis is a new species. E. histolytica, G. lamblia, A. lumbricoides, whipworm and pinworm were distributed nationwide, while Cysticercus (27 P/A/M), Taenia (27), hookworm (26), Balantidium coli (22), Clonorchis sinensis (22), Paragonimus westermani (21), H. diminuta (21), Echinococcus (18), H. nana (17), Fasciolopsis buski (16), T. spiralis (12) were distributed non-nationwide. A preliminary suggestion on intervention of the common and/or most detrimental parasitic diseases was submitted, including hydatidosis, taeniasis, cysticercosis, clonorchiasis, paragonimiasis, trichinellosis, hookworm disease, ascariasis, trichuriasis and enterobiasis.

Animals↗
PubMed1994

Nationwide survey of human parasite in China.

A nationwide survey of human parasites in China was conducted during 1988-1992, with a coverage of 30 provinces/autonomous regions/municipalities (P/A/M). A total of 2,848 pilot sites in 726 counties were selected by random sampling, and 1,477,742 individuals residing on were surveyed by fecal examination. The status of paragonimiasis, hydatid diseases, cysticercosis and trichinellosis were summarized through data review. The overall infection rate of intestinal parasites was 62.6% whereas at provincial level, the highest infection rate (94.7%) was recovered in Hainan, and the lowest (17.5%) in Heilong-jiang. A high proportion (43.3%) of polyparasitism among the infected population (882,080) was revealed. Altogether 56 species of parasites comprising protozoa (19), trematode (16), cestodes (8), nematodes (12) and thorny-headed worm (1) were discovered. During the survey a new species and several new records were documented. The number of the population infected with common intestinal parasites was estimated. The diversities of parasite distribution were noted in different nationalities as well as in varied occupations.

Adolescent↗
PubMed1994

Effects of erythropoietin on mobilisation of haemopoietic progenitor cells.

Peripheral blood progenitor cell (PBPC) mobilising regimens that do not include cytotoxic drugs are needed if PBPC are to be used for allogeneic transplantation. We have studied the effects of erythropoietin on bone marrow and circulating haemopoietic progenitors. Eleven patients with untreated lymphoma received epoetin-alpha 300 or 450 iu/kg subcutaneously (sc) thrice weekly for 2 weeks. Their bone marrows and peripheral bloods were normal at entry. There were no differences between dose levels. Peripheral blood colony-forming cell (CFC) numbers increased fivefold over baseline (p = 0.003) including a sevenfold increase in GM-CFC (p = 0.003). CD34-positive cell numbers increased 4.6-fold (P < 0.01). Maximal CFC release was seen at days 5-8. No consistent change in megakaryocyte numbers was seen. The increase in numbers of cells capable of long-term haemopoiesis was not significant. The ratio of myeloid:erythroid cells in bone marrow reduced from 2.7 to 0.86 after erythropoietin treatment (p = 0.047). In bone marrow the only significant rise in CFCs was in erythroid progenitors. Erythropoietin alone resulted in a modest increase in PBPC that is unlikely to be useful for transplantation. The effects of erythropoietin in combination with other cytokines or with cytotoxic drugs remain to be explored.

Adult↗
PubMed1993

Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis.

Myeloablative treatment and peripheral blood progenitor cell (PBPC) transplantation are increasingly used for lymphomas and leukemias. We have sought to optimize conditions for priming, collection, and engraftment of the leukapheresis product. Fifty-four consecutive adult patients were eligible, 31 with high-grade non-Hodgkin's lymphoma of poor prognosis, 12 with Hodgkin's disease in chemosensitive relapse, and 11 with poor prognosis acute lymphoblastic leukemia. Filgrastim was administered after routine chemotherapy with VAPEC-B or HiCCOM to mobilize PBPC. A rapidly increasing white blood cell count was used to predict the time of peak PBPC release and plan leukapheresis. Forty-five patients underwent leukapheresis. A median of 14 L of blood was processed at a single apheresis. A median of 2.4 x 10(8)/kg mononuclear cells (MNCs), 1.04 x 10(6)/kg granulocyte-macrophage colony-forming cells (GM-CFCs), and 10.6 x 10(6)/kg CD34+ cells were obtained. Slightly fewer MNCs were obtained from the heavily pretreated Hodgkin's disease group. There were no other significant differences in the size or composition of the leukapheresis harvest in the three patient groups. Forty patients underwent high-dose therapy and PBPC transplantation. Filgrastim was administered by daily subcutaneous injection until the absolute neutrophil count was > or = 1 x 10(9)/L for 2 consecutive days. Rapid and sustained hematopoietic engraftment occurred in all patients. The median time to achieve a neutrophil count > or = 0.5 x 10(9)/L was 9 days (range, 8 to 16 days); to achieve a platelet count > or = 20 x 10(9)/L was 10 days (range, 6 to 88 days); and to achieve a platelet count > or = 50 x 10(9)/L was 15.5 days (range, 10 to 100 days). Neutrophil recovery was faster than that of a historical control group treated with autologous bone marrow transplantation and filgrastim, but platelet recovery times were halved in the PBPC group. There was no secondary engraftment failure. Requirements for blood and platelet transfusions, antibiotic use, and parenteral nutrition were similar in the three patient groups. The median number of days in the hospital was 13 (range, 10 to 55) in the PBPC patients, compared with 19 (range, 14 to 51) in the historical controls. Leukapheresis yields (MNC, GM-CFC, and CD34+ cell numbers) were not useful for predicting the times to engraftment. We have shown that sufficient PBPC for transplantation can be obtained at a single leukapheresis after mobilization with routine chemotherapy and filgrastim in patients with non-Hodgkin's lymphoma, Hodgkin's disease, and acute lymphoblastic leukemia, even those heavily pretreated.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

A C. elegans mutant that lives twice as long as wild type.

We have found that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type. This lifespan extension, the largest yet reported in any organism, requires the activity of a second gene, daf-16. Both genes also regulate formation of the dauer larva, a developmentally arrested larval form that is induced by crowding and starvation and is very long-lived. Our findings raise the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation. daf-2 and daf-16 provide entry points into understanding how lifespan can be extended.

Animals↗