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Biomedical subjects

A Chang

Publications and source records attributed to A Chang.

At least 181 records · Page 10Linked to original sources
PubMed1994

American Public Health Association/American Academy of Pediatrics Injury Prevention Standards.

Injury prevention is an integral part of quality child-care programs. National standards relating to injury prevention have been published by the APHA and the AAP. The majority of these standards are preventive in nature and stress injury prevention in the development of policies and procedures and in the implementation of daily practices in child-care programs. Although it may not be possible to prevent all injuries in child-care settings, it is important for care givers, parents, and health professionals to identify potential hazards in the child-care environment. Once these hazards are identified, preventive corrective actions directed toward both environmental modifications and individual behaviors can be promoted to keep the incidence of injuries as low as possible.

Accident Prevention↗
PubMed1994

An international perspective on child day-care health.

If we are committed to the health and development of children, we need to recognize that the vast majority of the world's women are working women. In Africa, 80% of the women are actively engaged in economic activities outside the home. The "economic miracle" in Southeast Asia was made possible by the nimble fingers of thousands of women working in textile and electronics factories. There is need for pre-day-care advocacy for infants, through promotion of breast feeding and maternity leave. When the mother returns to work, the standard of the International Labor Organization should be applied, namely" ...the care of children while the parents are working cannot be ignored because it forms a focal point on which three main concerns of development policy--work, health, and education--converge." Several principles emerged from the presentations in the international panel: 1. Child-care programs must be community based, using the resources of the families and the community organizations themselves. 2. Programs require the active involvement of the communities, women's groups, and other partners. 3. Programs are modified by innovations created by community organizations, universities, and other groups. 4. Programs require the mobilization of trained young men and women into the field of early childhood education and development. This international panel provided an overall uniting theme, that throughout the world the hope for the survival and better life for children unites parents of every country and every creed. This is one of the most powerful and strongest motivational resources in the world.(ABSTRACT TRUNCATED AT 250 WORDS)

Canada↗
PubMed1994

Elevated susceptibility to 4-ipomeanol cytotoxicity in immature Clara cells of neonatal rabbits.

The bronchiolar Clara cell is one of the primary targets in adult mammals for environmental contaminants metabolized by cytochrome P450 (CYP) monooxygenases. Previous studies show that the onset of CYP expression in Clara cells occurs during postnatal lung development. This study was designed to determine whether differentiating Clara cells are susceptible to CYP-activated cytotoxicants and whether these substances can influence subsequent cytodifferentiation. Adult and neonatal (5-9 days of age) rabbits were given a single dose of 4-ipomeanol (IPO) i.p. and sacrificed 2 or 7 days later. Their lungs were removed and assessed morphologically, immunohistochemically or for CYP activity. Treatment with 10 mg/kg of IPO (0.25 of the LD50 for adults) killed 6 of 10 neonatal rabbits. At a dose of 5 mg/kg of IPO, most terminal bronchiolar cells were destroyed in the neonatal rabbits. The basal lamina of terminal bronchioles was either bare or lined by squamous or low cuboidal epithelium and macrophages. Terminal bronchiolar epithelium in neonates was minimally affected by a dose of 1 mg/kg of IPO. The terminal bronchioles in adults appeared nearly unaffected by either 1 or 5 mg/kg of IPO. Interalveolar septa were unaffected in all treated animals. Lung microsomal enzymes from neonatal rabbits metabolized IPO to reactive intermediates at less than one-third the rate in the lungs of adults. Seven days (15 days of age) after IPO treatment, CYP activity (as measured by pentoxyresorufin O-dealkylation) was one-half that of age-matched controls after a dose of 5 mg/kg but equaled control activity after 1 mg/kg. Immunohistochemical analysis, using antibodies to CYP2B4, CYP4B and CYP reductase, indicated that the decrease in activity seen with a dose of 5 mg/kg of IPO was the result of a loss of immunoreactive CYP proteins from the cuboidal cells of terminal bronchioles. It was concluded that, in neonatal animals, differentiating Clara cells are more susceptible to injury by bioactivated cytotoxicants than are differentiated cells in adults, despite the neonate's lower levels of CYP monooxygenases. Furthermore, IPO-induced injury impairs the normal pattern of postnatal Clara cell differentiation.

Aging↗
PubMed1994

Metabolism and cytotoxicity of naphthalene and its metabolites in isolated murine Clara cells.

Nonciliated bronchiolar epithelial (Clara) cells of mice are highly susceptible to toxicants that undergo metabolic activation, presumably because this cell type expresses high levels of cytochrome P450 monooxygenases. To establish the capability of these cells to metabolize an agent that causes Clara cell-selective toxicity in vivo, we evaluated the metabolism of naphthalene in isolated cells under two distinct conditions, i.e., in homogenized cell preparations supplemented with glutathione and glutathione S-transferases and in intact cells. In homogenized cell preparations naphthalene was metabolized to dihydrodiol (minor) and a single glutathione adduct (major) derived from the 1R,2S-epoxide. In intact cells the rate of formation of glutathione adduct was much lower and dihydrodiol predominated. Approximately 3-10% of racemic naphthalene oxide added to isolated homogenized cells was converted to glutathione adducts and dihydrodiol in 3-min incubations. At high concentrations of naphthalene oxide (0.25 and 0.5 mM), formation of the adduct derived from the 1R,2s-epoxide was favored. The intracellular glutathione concentration, measured by high performance liquid chromatography as the fluorescence of the monobromobimane-glutathione derivative, was 1.14 +/- 0.13 nmol/10(6) cells. To determine whether Clara cell injury results from cytotoxic metabolites of naphthalene, we assessed viability of intact cells in response to different concentrations of naphthalene and naphthalene metabolites. At high naphthalene concentrations (0.5 and 1.0 mM) cell viability decreased to 63% or less of control, whereas lower concentrations (0.1 or 0.05 mM) did not alter viability significantly. Naphthalene-induced decreases in cell viability were blocked by preincubation of Clara cells with the cytochrome P450 monooxygenase inhibitor piperonyl butoxide. The cytotoxicity of naphthalene metabolites varied. Incubation of cells with 0.5 mM dihydrodiol, 1-naphthol, or 1,2-naphthoquinone decreased cell viability to an extent similar to that produced by 0.5 mM naphthalene. In contrast, 0.5 mM naphthalene oxide and 1,4-naphthoquinone significantly decreased viability more than the parent compound. Preincubation of Clara cells with piperonyl butoxide did not affect the loss in cell viability associated with naphthalene oxide. We conclude that isolated Clara cells 1) are capable of metabolizing naphthalene, a Clara cell-specific cytotoxicant, to two major metabolites, 2) have a detectable intracellular glutathione pool, and 3) are more susceptible to specific naphthalene metabolites than to the parent compound naphthalene.

Animals↗
PubMed1993

Folding and intracellular transport of the yeast plasma-membrane H(+)-ATPase: effects of mutations in KAR2 and SEC65.

We have developed two independent assays to study the integration, folding, and intracellular transport of the polytopic plasma membrane H(+)-ATPase in yeast. To follow folding, controlled trypsinolysis was used to distinguish between the E1 conformation of the ATPase (favored in the presence of ADP) and the E2 conformation (favored in the presence of vanadate). By this criterion, wild-type ATPase appears to recognize its ligands and assume distinct conformations within a short time after its biosynthesis. To follow intracellular transport, we have exploited the fact that export of newly synthesized ATPase from the endoplasmic reticulum is accompanied by kinase-mediated phosphorylation, leading to a shift in electrophoretic mobility. Because proper folding is required for transport from the endoplasmic reticulum, the mobility shift also serves as a convenient bioassay for correct folding. As a first step toward identifying cell components important in folding of the nascent ATPase, we have used the dual assays to examine the role of KAR2, encoding the yeast homolog of immunoglobulin heavy chain binding protein/78-kDa glucose-regulated protein, and SEC65, encoding a subunit of the yeast signal recognition particle. Although mutation of KAR2 caused defective translocation of several secretory precursors into the endoplasmic reticulum lumen, ATPase folding and intracellular transport were unperturbed. By contrast, in a sec65 mutant, the folding and intracellular transport of newly synthesized ATPase were delayed. Our data suggest that conformational maturation of the ATPase is a rapid process in wild-type cells and that membrane integration mediated by signal recognition peptide is important for the proper folding of this polytopic protein.

Cell Membrane↗
PubMed1993

Efficacy of oral ondansetron in the prevention of emesis in outpatients receiving cyclophosphamide-based chemotherapy. The Ondansetron Study Group.

OBJECTIVE: To evaluate the efficacy and safety of oral ondansetron (Zofran) as an antiemetic in patients receiving cyclophosphamide-based chemotherapy. DESIGN: A multicenter, randomized, double-blind, stratified, placebo-controlled trial conducted between March 1989 and January 1990. SETTING: Twenty-seven oncology centers including university hospitals, community cancer centers, and private medical oncology practices. PATIENTS: A total of 349 chemotherapy-naive patients having their first cycle of cyclophosphamide (> or = 450 mg/m2)-based chemotherapy. Patients also received methotrexate (> or = 30 mg/m2) or doxorubicin (> or = 35 mg/m2). All patients were evaluated for safety and 318 (91%) were evaluated for efficacy. INTERVENTIONS: Patients were randomly assigned to one of four treatment groups: placebo, 1 mg, 4 mg, or 8 mg of ondansetron. Assigned study medication was taken three times per day for 3 consecutive days. MEASUREMENTS: Time and number of emetic episodes as well as degree of nausea were recorded by patients for each of the 3 study days. RESULTS: Compared with placebo, all three doses of ondansetron were superior (P < 0.001) in preventing vomiting and controlling nausea. A complete response (no emetic episodes) was observed in 19%, 57%, 65%, and 66% of patients in the placebo, 1-mg, 4-mg, and 8-mg ondansetron groups, respectively. For patients who received higher-dose cyclophosphamide and doxorubicin, a dose-related trend in antiemetic efficacy of ondansetron was observed. Mild headache and constipation were the most frequently reported adverse events. No extrapyramidal reactions were observed. CONCLUSION: Oral ondansetron is a safe and effective antiemetic that is more efficacious than placebo for patients receiving cyclophosphamide-based chemotherapy.

Administration, Oral↗
PubMed1993

Phase II trial of carboplatin in patients with metastatic malignant melanoma. A report from the Eastern Cooperative Oncology Group.

Thirty patients with pathologically proven, measurable metastatic melanoma without prior chemotherapy were treated with carboplatin 400 mg/m2 by intravenous infusion for 30 minutes every 4 weeks. Twenty-seven patients were evaluable for response and toxicity. Two complete responses and one partial response (3 of 27 = 11%, 90% confidence intervals: 3-26%) were documented. The median survival was 4.7 months. The most common toxicity was myelosuppression. One drug-related death was observed due to renal failure. Prior radiotherapy and liver metastasis were the poor prognostic indicators identified in our study. Carboplatin in the dose and schedule reported in our trial has only modest antitumor activity in patients with advanced malignant melanoma.

Adult↗
PubMed1993

Activation of the complement system in baboons challenged with live Escherichia coli: correlation with mortality and evidence for a biphasic activation pattern.

Activation of the complement system was studied in baboons that were challenged with live Escherichia coli. In the group challenged with a lethal dose (n = 4), the complement activation parameters C3b/c, C4b/c, and C5b-9 increased 13, 5, and 12 times the baseline value, respectively, during the first 6 h after the E. coli infusion, whereas in the group challenged with a sublethal dose (n = 10), they increased only moderately, by 2 to 3 times the baseline value. However, in this latter group, a more pronounced activation occurred at 24 h. Subsequent experiments showed that this second phase in complement activation started at 6 h after the challenge, at which time infused microorganisms had been cleared from the circulation. The simultaneous increase in C-reactive protein with this second phase suggested an endogenous activation mechanism involving this acute-phase protein. Levels of inactivated (modified) C1 inhibitor also increased in both groups, with peak levels of 2.5 times the baseline value at 24 h in the sublethal group and of 4 times at 6 h after the challenge in the lethal group. Thus, activation of complement in this animal model for sepsis occurs in a biphasic pattern, the initial phase mediated by the bacteria and the later phase mediated by an endogenous mechanism possibly involving C-reactive protein. The differences in complement activation between animals with lethal or sublethal sepsis support the hypothesis that complement activation contributes to the lethal complications of sepsis.

Animals↗
PubMed1993

Alpha-2-macroglobulin functions as an inhibitor of fibrinolytic, clotting, and neutrophilic proteinases in sepsis: studies using a baboon model.

Alpha-2-macroglobulin (alpha 2M) may function as a proteinase inhibitor in vivo. Levels of this protein are decreased in sepsis, but the reason these levels are low is unknown. Therefore, we analyzed the behavior of alpha 2M in a baboon model for sepsis. Upon challenge with a lethal (4 baboons) or a sublethal (10 baboons) dose of Escherichia coli, levels of inactivated alpha 2M (i alpha 2M) steadily increased, the changes being more pronounced in the animals that received the lethal dose. The rise in i alpha 2M significantly correlated with the increase of thrombin-antithrombin III, plasmin-alpha 2-antiplasmin, and, to a lesser extent, with that of elastase-alpha 1-antitrypsin complexes, raising the question of involvement of fibrinolytic, clotting, and neutrophilic proteinases in the inactivation of alpha 2M. Experiments with chromogenic substrates confirmed that thrombin, plasmin, elastase, and cathepsin G indeed had formed complexes with alpha 2M. Changes in alpha 2M similar to those observed in the animals that received E. coli occurred in baboons challenged with Staphylococcus aureus, indicating that alpha 2M formed complexes with the proteinases just mentioned in gram-positive sepsis as well. We conclude that alpha 2M in this baboon model for sepsis is inactivated by formation of complexes with proteinases, derived from activated neutrophils and from fibrinolytic and coagulation cascades. We suggest that similar mechanisms may account for the decreased alpha 2M levels in clinical sepsis.

Animals↗
PubMed1993

The immunohistochemical effect of a hydrocolloid occlusive dressing (DuoDERM E) in psoriasis vulgaris.

The topical application of a hydrocolloid occlusive dressing (HCD) has been shown in various studies to have an antipsoriatic effect as monotherapy but especially in combination with a topical corticosteroid. The aim of the present study was to assess the effect of 3 weeks of HCD monotherapy at the immunohistochemical level. Ten patients were treated. Before and after treatment, a biopsy was taken, and immunohistochemical stainings were carried out with markers for epidermal growth, keratinization, inflammation and endothelium. Suprabasal expression of keratin 16, the number of cycling epidermal cells and the number of polymorphonuclear leucocytes and T lymphocytes tended to decrease during treatment. The endothelial markers did not change during HCD treatment. This study confirms the antipsoriatic effect of HCD and demonstrates that its effect upon some markers of inflammation, epidermal proliferation and keratinization is modest.

Adult↗
PubMed1993

The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons.

The hypotension and disseminated intravascular coagulation (DIC) in bacteremia is thought to be mediated by the combined actions of cytokines, prostaglandins, and complement. The contact system, via the release of bradykinin and the activation of Factor XI, has been postulated to be contributing to the observed hypotension and DIC. Using a mAb to Factor XII (C6B7), we blocked the activation of the contact system in an established experimental baboon model in which Escherichia coli was infused to produce lethal bacteremia with hypotension. The untreated group (n = 5) displayed contact activation, manifested by a significant decrease in high molecular weight kininogen (HK) and a significant increase in alpha 2 macroglobulin-kallikrein complexes (alpha 2M-Kal). The C6B7-treated group (n = 5) showed an inactivation of Factor XII and the changes in HK and alpha 2M-Kal complexes were prevented. Both groups developed DIC manifested by a decrease in platelet, fibrinogen, and Factor V levels. The untreated group developed irreversible hypotension. The treated group experienced an initial hypotension that was reversed and extended the life of the animals. This study suggests that irreversible hypotension correlates with prolonged activation of the contact system, and specific antibody therapy can modulate both the pathophysiological and biochemical changes.

Animals↗