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Biomedical subjects

M J Chang

Publications and source records attributed to M J Chang.

At least 55 records · Page 3Linked to original sources

A non-invasive monitoring of exposure to an industrial organic solvent, dimethylformamide.

A urinary metabolite, N-hydroxymethyl-N-methyl formamide (DMF-OH) was measured by a colorimetric method in Wistar and Sprague-Dawley rat urine after a single exposure to N,N-dimethyl formamide (DMF). A linear relationship was found between the total excretion of DMF-OH in 2 days versus the exposure ranging from 1 to 20% of the LD50 of DMF i.e. 47.2 to 944 mg DMF per kg b. wt. This is proposed to be a non-invasive biological method for monitoring exposure to DMF.

Animals↗

Immunotherapeutic approaches to leukemia: the use of the Friend virus-induced erythroleukemia model system.

We have developed a model system to study immunologically mediated regression of leukemia based on Friend virus-induced erythroleukemias. This system has been used to evaluate the immunotherapeutic activity of macrophages, specifically reactive T-cells (CTL/RFB), lymphokine-activated killer cells and interleukin 2, and tumor necrosis factor alpha and interferon-gamma. In the present studies, CTL/RFB were evaluated for their ability to prevent disease recurrence. Animals with the regressing strain of Friend virus at Day 39 post virus were treated with either one or two injections of 5 x 10(6) CTL/RFB. Animals given one or two injections of CTL/RFB had a significantly lower rate of recurrence than did untreated animals. The helper T-cell component of CTL/RFB was implicated in causing leukemia regression. Interleukin 1 alpha and tumor necrosis factor alpha, multifunctional cytokines with similar biological activities, were evaluated for their ability to suppress leukemic erythroid colony-forming cells and induce regression. Interleukin 1 alpha suppressed the conventional strain of, but not the polycythemia-inducing strain of, Friend virus-leukemic late erythroid colony-forming units and caused only a temporary regression of disease, while tumor necrosis factor alpha suppressed both forms of the disease and with multiple inoculations could cause permanent disease regressions. This system provides an excellent model for examining the efficacy of immunotherapy of leukemias with various mediators and effector mechanisms.

Animals↗

A technique for monitoring mammalian cell growth and inhibition in situ via Fourier transform infrared spectroscopy.

A single culture of Chinese hamster ovary cells was grown on germanium attenuated total reflectance (ATR) crystals and continuously monitored in situ via ATR/Fourier transform infrared (FT-IR) spectroscopy for approximately 60 h. The cells were seeded into a specially designed flow cell which controlled physiological conditions, flow rate, and addition of growth medium or metabolic inhibitors. Infrared spectra were taken at 20-min intervals until a confluent monolayer was formed. Several strong bands are evident in the spectra which can be generally ascribed to molecular features of cellular components. Cell growth kinetics were measured as a function of infrared band intensity over time and exhibited the normal lag phase, logarithmic growth, and stationary phase on reaching confluence. Spectra of growing cells, normalized to the area under the spectral region 1800-1000 cm-1, were subtracted from reference spectra of confluent cells at 60 h. Difference spectra showed that the largest differences were observed between confluent cells and cells in early growth stages. Differences may reflect cell morphological changes, biochemical activity, and degree of ATR crystal exposure to the bulk medium. ATR/FT-IR spectroscopy of living Chinese hamster ovary cells was also used in a toxicological study to monitor the effects of hydroxyurea, an inhibitor of DNA synthesis. Delayed growth was observed in the cell growth curve of the hydroxyurea-treated cells during the course of treatment as compared to the control culture.

Animals↗

In vivo hematopoietic effects of tumor necrosis factor-alpha in normal and erythroleukemic mice: characterization and therapeutic applications.

The effects of recombinant, macrophage-derived, murine tumor necrosis factor-alpha (TNF-alpha) on hematopoiesis in vivo has been examined in normal mice and in Friend virus (FV)-induced erythroleukemic mice. Intravenous (IV) administration of a single dose of recombinant murine TNF-alpha (10(5) U per mouse) significantly suppressed normal and leukemic late-stage erythropoiesis as measured by numbers of mature erythroid colony forming cells (CFU-E) in the bone marrow and spleen and by peripheral blood reticulocyte counts. In normal animals, the immature erythroid (BFU-E), macrophage (CFU-M), and granulocyte-macrophage (CFU-GM) compartments were significantly stimulated by TNF-alpha in both the bone marrow and the spleen. In the bone marrow of leukemic mice, the BFU-E, CFU-GM, and CFU-M progenitor cell compartments were also stimulated by treatment with the monokine. In the spleens of leukemic mice (the primary site of FV leukemia cell accumulation), relative numbers of BFU-E and CFU-GM were increased by TNF-alpha, while those of CFU-M were suppressed. TNF-alpha caused a rapid decrease in the markedly elevated spleen weights of progressively leukemic mice, and in multiple doses it caused complete clinical disease regression in a significant percentage of leukemic animals. The combination of TNF-alpha with interferon-gamma (IFN-gamma) increased the incidence of leukemia regression, compared with TNF-alpha alone. These results show that TNF-alpha exerts a suppressive influence on late-stage erythropoiesis in vivo and suggest that this effect might be exploited in the treatment of acute erythroleukemia, erythroid hyperplasias, and related diseases.

Animals↗

Pleural empyema in children: a nationwide retrospective study.

Military hospitals across the United States provided data for this study on pediatric patients with pleural empyema. Haemophilus influenzae type b (17%), Streptococcus pneumoniae (14%), and Staphylococcus aureus (11%) were the most common etiologic agents. Male patients predominated, except among blacks. The mortality was high in patients with hospital-acquired empyemas.

Adolescent↗

Age-sensitive morphologic changes in tracheal organ culture following carcinogen exposure.

This study was designed to assess the differential sensitivity of tracheal explants obtained from female golden Syrian hamsters at 30, 100, or 180 days of age to exposure to crocidolite asbestos or benzo[a]pyrene (BaP). Explants were evaluated at 1 or 4 weeks following the initial exposure. Hyperplasia and squamous metaplasia of the mucosal epithelium were observed in exposed explants. Alcian blue-periodic acid-Schiff base stains demonstrated decreased amounts of intracellular acidic mucopolysaccharides in exposed explants. Morphometry supported the qualitative observations that lesions were more severe in tracheas from 30-day-old animals than lesions from the 100- and 180-day-old donor hamsters. Thus, it appears that the age-dependent, early toxic response of the tracheal organ culture model to carcinogens parallels that of animal models.

Aging↗

Erythromycin-sulfisoxazole vs amoxicillin in the treatment of acute otitis media in children. A double-blind, multiple-dose comparative study.

A fixed combination of erythromycin ethylsuccinate and sulfisoxazole acetyl (erythromycin-sulfa) was compared with amoxicillin for the treatment of acute otitis media (AOM) in children. Of 145 patients studied, 76 boys and 69 girls were compliant and were evaluated for drug efficacy (72 amoxicillin, 73 erythromycin-sulfa). Based on otoscopic and tympanometric results, cure rates at ten to 14 days for AOM due to all organisms were 83% (63/72) for amoxicillin and 89% (65/73) for erythromycin-sulfa; for Haemophilus species (including mixed infections), they were 84% for amoxicillin (26/31) and 83% for erythromycin-sulfa (20/14). Cure rates for ampicillin-resistant Haemophilus were 1/1 for amoxicillin and 7/8 (88%) for erythromycin-sulfa; one patient (12%) had persistent AOM at day 10. Of the patients with AOM due to Streptococcus pneumoniae, 82% (29/35) in the amoxicillin-treated group and 98% (39/40) in the erythromycin-sulfa-treated group were cured. Patients with S pneumoniae as the initial infecting organism who were treated with amoxicillin had significantly more clinical recurrences then their erythromycin-sulfa-treated counterparts, 66% (8/12) vs 33% (3/9). There was no difference between treatment groups in recurrence rates for patients with Haemophilus as the initial infecting organism. On the treatment day indicated, the following number of patients had middle ear effusion: by days 10 to 14, 38% (27/72) amoxicillin-treated patients and 48% (35/73) erythromycin-sulfa-treated patients; by day 28, 10% (7/71) amoxicillin-treated patients and 16% (11/70) erythromycin-sulfa-treated patients. There were no significant differences in adverse reactions. The erythromycin-sulfa combination is safe and effective treatment for AOM, including ampicillin-resistant Haemophilus.

Acute Disease↗

Ten-minute detection of group A streptococci in pediatric throat swabs.

A 10-min latex agglutination test kit, Culturette Brand Ten-Minute Group A Strep ID (Marion Scientific, Div. of Marion Laboratories, Inc., Kansas City, Mo.), was assessed for the rapid detection of group A beta-hemolytic streptococcus directly from a throat swab. Four hundred and thirty-five throat swab specimens from children with suspected group A streptococcal infection were tested by the Ten-Minute Group A Strep ID and by concurrent conventional culture. The strep test was effective in detecting group A streptococcal infection; 90% (63/70) of culture-positive specimens gave positive latex tests. The specificity of the test was 99.2% (362/365). The predictive values were 95.5% for positives and 98.1% for negatives. Overall agreement with culture was 98% (425/435). This test offers a sensitive and specific method for the early detection of group A beta-hemolytic streptococci in throat swabs of children and would be most useful in a hospital laboratory or pediatrician's office.

Adolescent↗

Induction of single-strand breaks plus alkali-labile bonds by N-nitrosoureas in rat tissues in vivo: ethylnitrosourea versus benzylnitrosourea.

Alkaline sucrose sedimentation procedures were used to quantitate the amount of single-strand breaks plus alkali-labile bonds (SSB + ALB) induced and repaired following a single intraperitoneal injection of the neurocarcinogen N-ethyl-N-nitrosourea (ENU) and its non-neurocarcinogenic analog N-benzyl-N-nitrosourea (BNU) in the brain, liver and kidney of female Sprague-Dawley rats. SSB + ALB were measured and used as an indicator of apurinic/apyrimidinic sites, phosphotriesters and in situ breaks. ENU induced a dose-dependent increase in the number of SSB + ALB at the doses studied (0, 0.39, 0.77, 1.54 mmoles/kg) in all 3 tissues. At 1 h postinjection with 0.77 mmoles/kg of these compounds there were 50-70% fewer breaks induced by BNU than ENU. The SSB + ALB induced by ENU persisted over a 7-day period, while those induced by BNU did not. Thus, these studies showed that 2 homologues of nitrosoureas, ENU and BNU, exhibited different potentials to induce and to persist SSB + ALB in vivo.

DNA↗

The measurement of sister chromatid exchanges induced in utero utilizing intraperitoneal infusion of BrdU: a novel technique.

One of the inherent difficulties associated with the accurate detection of sister chromatid exchanges (SCE's) in vivo is the maintenance of a continuous supply of 5-bromo-2'-deoxyuridine (BrdU) for differential staining of sister chromatids. We have developed a simple, reproducible intraperitoneal technique which has the advantages of continuous BrdU infusion and is less stressful than presently available methods. Additionally, a gentle trypsinization methodology was developed to obtain relatively large numbers of metaphases from fetal tissues. Using these techniques, we examined the induction of SCE by 7,12-dimethylbenz(a)anthracene (DMBA) when injected into pregnant CD rats on days 11, 13, 15, and 16 of gestation. The levels of SCE induced were slightly higher in fetal than maternal tissue, although not significantly.

9,10-Dimethyl-1,2-benzanthracene↗

Characterization of cytotoxic effect of asbestos on normal human fibroblasts.

Using viable cell counting and the incorporation of radioactive thymidine in cell TCA precipitate, we have attempted to separate the effects of asbestos on cell growth inhibition (reproductive failure) vs. cell killing. NIEHS crocidolite and NIEHS intermediate-sized chrysotile at a concentration of 10 micrograms/mL were studied. Cytotoxic effects were demonstrated with both types of asbestos. Thymidine incorporation expressed as cpm/viable cell was enhanced in the presence of either form of asbestos. It is concluded that both negatively charged crocidolite and positively charged chrysotile are toxic to human fibroblast cells in culture and exert their cell killing but not growth inhibition effect concurrently with a stimulation of DNA synthesis.

Asbestos↗

Effects of chrysotile co-exposure on BaP binding in normal human fibroblasts.

The effects of chrysotile and benzo(a)pyrene (BaP) co-exposure on uptake, metabolism and BaP binding to nucleic acids were investigated in normal human fibroblasts. A significant enhancement in these parameters was found when co-exposure was carried out under serum-free conditions. In the presence of serum, only a slight enhancement of BaP uptake was detected, while metabolism and binding to nucleic acids were not affected over the 8-hr incubation period studied.

Asbestos↗

Thermal modification of chrysotile asbestos: evidence for decreased cytotoxicity.

Many asbestiform minerals exhibit temperature-dependent thermoluminescence. Since thermoluminescence involves electronic transitions within crystalline materials, the effect of temperature on asbestos cytotoxicity was evaluated. Heat pretreatment of Canadian chrysotile asbestos reduces its cytotoxicity towards cultured human fibroblasts and bovine alveolar macrophages. When monitored 44 hr after the addition of either 200 degrees C or 400 degrees C heat-pretreated asbestos, alveolar macrophage viability was approximately 40% higher than comparable amounts of unheated asbestos. Similarly, asbestos toxicity, expressed as fibroblast growth inhibition, was inversely related to the asbestos pretreatment temperature in the following manner, 70 degrees C greater than 200 degrees C greater than 400 degrees C = unexposed fibroblast controls. Pretreatment of chrysotile asbestos to 400 degrees C reduced its adsorptive capacity for bovine serum albumin by 25%. Furthermore, asbestos heated to 200 degrees C followed by irradiation with 4 MeV X-rays (4500 rads) resulted in reactivation of asbestos cytotoxicity. Scanning electron microscopy indicated that the ratios of free to fiber-associated alveolar macrophages and the fiber fragment size distributions were unaffected by either heat pretreatment or X-ray irradiation. These observations strongly suggest that the surface charge characteristics and electronic state of asbestos fibers may be responsible for its biological activity.

Adsorption↗

Interrelationships between cellular proliferation, DNA alkylation and age as determinants of ethylnitrosourea-induced neoplasia.

Thirty-day-old Sprague--Dawley rats were used to study the persistence of DNA lesions (e.g., O6-alkylguanine) induced by various doses of ethylnitrosourea (ENU). Cellular proliferation was measured as an increment of DNA content per organ at 7 days post-treatment. We observed that the persistence of O6-EtGua was not affected by the various dose levels. Comparing the 3 organs, the persistence of O6-EtGua ranked in the order of brain greater than kidney greater than liver, while the percent increase in DNA content was measured as liver greater than kidney greater than brain. When the target specificity of ENU carcinogenesis in 30-day-old rats was compared to that following transplacental exposure in terms of its relationship to the persistence of DNA lesions and the rate of target cellular proliferation, it permitted the conclusion that induction of neoplasia in target cells is not only determined by persistent DNA lesions but also by the rate of proliferation of target cells at the time of exposure.

Age Factors↗

Haemophilus influenzae biotype III infections in children and report of three unusual cases.

Three hundred thirty seven Haemophilus influenza isolates from infections in children were studied to determine the relationship between H. influenza, biotype III, and specimen source. Eighteen per cent (60) of the isolates were H. influenza biotype III. Of these, 70% were from the eye, 18% from the respiratory tract, 7% from the ear and 2% from blood. Although conjunctivitis was the most common clinical condition associated with H. influenza biotype III, three cases of systemic infection with this organism are presented: a 10-month-old female with pneumonia, a 17-year-old male with sepsis, and a 7-year-old male with endophthalmitis. This organism may be a significant pathogen depending on the clinical setting. Increased awareness of its importance will lead to more reports of its isolation.

Adolescent↗

Ampicillin-resistant Hemophilus influenzae type B septic arthritis in children.

Three cases of ampicillin-resistant Hemophilus influenzae type B septic arthritis are described. These patients presented over a four-month period (November 1978 to February 1979). All were less than 18 months of age, all had positive blood and joint aspirate cultures, and counter-current immunoelectrophoresis (CIE) on serum positive for Hemophilus influenzae type B. The ampicillin minimum inhibitory concentration (MIC) for all three isolates was 6.25 microgram/ml or greater. All patients recovered uneventfully with intravenous chloramphenicol therapy. We suggest that chloramphenicol be considered in the initial therapy of children under 18 months of age who present with septic arthritis, at least in geographic areas where the incidence of ampicillin resistance is high.

Ampicillin↗