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Biomedical subjects

M J Chang

Publications and source records attributed to M J Chang.

70 records · Page 4Linked to original sources
PubMed1981

Analysis of alkylated sites at N-3 and N-7 positions of purines as an indicator for chemical carcinogens.

This study reports a rapid assay to distinguish depurination from other forms of alkaline-labile lesions induced in DNA by alkylating agents. Covalently closed circular duplex PM2 DNA was treated with various alkylating agents such as N-methyl-N-nitrosourea, dimethyl sulfate, methyl methanesulfonate, N-ethyl-N-nitrosourea, diethyl sulfate, and ethyl methanesulfonate at pH 6.5. Apurinic sites and subsequent strand breaks were introduced by the hydrolysis of the alkylated purines under nondenaturing conditions by heating alkylated DNA at 70 degrees for 1.5 hr with 0.05 M 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid:KOH (pH 7.4), 0.1 M KCl, 0.01 M MgCl2, 0.0005 M ethylenediaminetetraacetate, 0.05 M glycine, and 0.01 M putrescine. The number of strand breaks produced, representing the alkylated sites at N-3 and N-7 positions of purines, were quantitated by electrophoresis in 1% neutral agarose slab gels. These results were compared with previously reported carcinogenic and mutagenic effects of these compounds, and a correlation between the apurinic sites, the total alkylated sites, and the biological effect of the alkylating agent was determined.

Alkylating Agents↗
PubMed1980

Retention of promutagenic O6-ethylguanine in the DNA of various rat tissues following transplacental inoculation with ethylnitrosourea.

Pregnant Fischer rats at their 20th day of gestation were inoculated intravenously with [14C]ENU (75 mg/kg). The O6-ethylguanine content of liver, kidney, and brain DNA from both fetuses (offspring) and adults were quantitatively determined 3 h and 7 days after carcinogen treatment. Removal of O6-ethylguanine from the DNA of brain (target) was much slower than from liver (non-target) and kidney (low-target). Retention of O6-ethylguanine was found to be relatively similar in adult and fetal brains, although 100% of the offspring transplacentally exposed to 75 mg/kg ENU were shown to develop tumors of the nervous system, whereas the inoculated pregnant dams did not.

Alkylation↗
PubMed1978

Diphenylhydantoin teratogenicity in man.

A case is presented of fetal teratogenic damage from an unusually high maternal dosage of diphenylhydantoin, 600 mg daily, to a 40-kg woman throughout pregnancy. The anomalies included narrowed ends of the fingers and toes; aplasia of the nails on the other fingers and toes; aplasia of the distal phalanges of the fingers and toes; a broad, depressed nasal bridge; anteverted nostrils; prominent upper lip; coarse, profuse scalp hair; pilonidal sinus; and simian crease of the left hand. At the age of 7 months, ossification of the distal phalanges of both middle fingers appeared, the anterior fontanel was small, brain development was retarded, cranial asymmetry was marked, and the fingertips showed a pattern of low arch dermal ridges.

Abnormalities, Drug-Induced↗
PubMed1977

Trimethoprim-sulfamethoxazole compared to ampicillin in the treatment of shigellosis.

Twenty hospitalized children between 1 and 11 years of age were enrolled in a comparative randomized evaluation of trimethoprim-sulfamethoxazole (TM-SM) and ampicillin for the treatment of shigellosis. Each drug was provided for five days. The group treated with ampicillin had significantly more stools per day (mean 21.25) compared to the TM-SM group (8.64). Treatment with TM-SM appeared to be associated with a more rapid reversion of stool cultures to normal, but these differences compared to ampicillin were not statistically significant. Review of all isolates of Shigella from our hospital revealed a marked decrease in sensitivity to ampicillin over the last six years. This pattern has been observed in other centers. TM-SM may be the best drug for the treatment of shigellosis in areas where multiple antibiotic-resistant organisms are common.

Ampicillin↗
PubMed1976

Prospective evaluation of treatment of Hemophilus influenzae meningitis.

Fifty children with Hemophilus influenzae meningitis have been enrolled in a prospective study. Patients were randomly assigned chloramphenicol or ampicillin treatment; there were no significant differences between groups in other respects. Countercurrent immunoelectrophoresis proved to be a valuable tool for rapid diagnosis of the causative agent even in pretreated patients. Increasing quantities of capsular polyribosephosphate antigen detected in the initial cerebrospinal fluid correlated significantly (r=0.62419; p less than 0.01) with early and late sequelae of meningitis. None of the patients died. Severe and persistent neurologic or intellectual deficits were noted in four (8%) of the children, and an additional 14 (28%) had IQ scores between 70 and 90. The presence of bactericidal antibody in serum was not protective. Anti-PRP antibody generally was not present in acute serum specimens and irrespective of the quantity of antigenic stimulus provided by the disease was nondetectable in 21 of 24 children less than 17 months of age following recovery.

Adolescent↗
PubMed1976

Cephalexin compared to ampicillin treatment of otitis media.

Cephalexin was compared to ampicillin for the treatment of otitis media in a randomized study. Bacteriologic diagnosis was sought by needle tympanocentesis in 179 children. No overall statistically significant differences were noted between the two groups; however, 20 patients who received cephalexin had a poor response to therapy whereas only five recipients of ampicillin responded poorly. A significant difference (P less than .05) between the two regimens was noted when Hemophilus influenzae was recovered. Fifty per cent of the children with H. influenzae otitis media who were treated with cephalexin responded poorly; no patients receiving ampicillin had a poor response. Our data suggest that the use of cephalexin monohydrate is not warranted for treatment of otitis media due to H. influenzae even when the isolate proves sensitive to this drug in vitro. In selected patients with otitis media caused by Staphylococcus aureus which is resistant to penicillin, cephalexin may provide effective treatment.

Ampicillin↗
PubMed1975

Kanamycin and gentamicin treatment of neonatal sepsis and meningitis.

Mortality from neonatal meningitis due to gram-negative microorganisms remains 50% despite use of aminoglycoside antibiotics. Blood was obtained on 238 occasions from 77 neonates with putative or documented sepsis; paired blood and cerebrospinal fluid (CSF) samples were obtained on 14 occasions from ten neonates with meningitis. Kanamycin and gentamicin were measured by a radioisotopic assay procedure. Kanamycin was administered at 15 mg/kg/day in three divided doses intravenously; serum concentrations peaked at one hour (mean, 7.77mug/ml). Gentamicin was administered at 7.5 mg/kg/day in three divided doses intravenously; serum concentrations peaked at two hours (mean, 5.34mug/ml). Both aminoglycosides generally were nondetectable within the CSF; survival of neonates with gram-negative meningitis correlated specifically with the sensitivity of their isolates to ampicillin which was administered concurrently. This study suggests that alternative approaches to the treatment of neonatal sepsis should be explored; administration of an antibiotic which crosses the blood-cerebrospinal fluid barrier more readily should be considered.

Aminoglycosides↗
PubMedDate not supplied

Exposure to epichlorohydrin and dimethylformamide, glutathione S-transferases and sister chromatid exchange frequencies in peripheral lymphocytes.

Workers in epoxy resin, synthetic leather, and printed circuit board manufacturing plants are exposed to epichlorohydrin (ECH), or dimethylformamide (DMF), or both. ECH, an alkylating agent, has been shown to cause malignancy in animals, but its genotoxicity in humans is unclear. DMF is a well-known hepatotoxic chemical, although evidence of its genotoxicity in humans is also limited. In this study, we examined the effects of exposure to ECH and DMF on sister chromatid exchange (SCE) in plant workers, in order to examine the genotoxicity of these two agents. Because the genotoxicity of certain agents can be modulated by metabolic traits, we also investigated influence of the glutathione S-transferase (GST) micro (GST M1) and GST theta (GST T1) genes on the genotoxicity of ECH and DMF. A total of 85 male plant workers were included in this study. The subjects were divided into five exposure groups, based on their job titles and the airborne ECH and DMF concentrations in their areas of work. A questionnaire was administered to obtain detailed occupational, smoking, alcohol consumption, and medication histories. Standardized cytogenetic methods were used to determine the frequency of sister chromatid exchange (SCE) in peripheral blood lymphocytes. GST M and GST T1 genotypes were identified using polymerase chain reaction (PCR). In analysis, smoking was significantly associated with increased SCE frequency (P<0.01). Workers with high ECH exposure also had significantly higher SCE frequencies than those with low or no ECH exposure (P<0.05). However, DMF exposure was not associated with SCE frequency. The GST M1 null genotype was also found to be associated with an increased SCE frequency (P = 0.06). We conclude that ECH exposure may be associated with genetic toxicity and that DMF does not appear to be genotoxic.

Adult↗
PubMedDate not supplied

Chlamydia trachomatis in otitis media in children.

Thirty-one middle ear fluids were obtained for Chlamydia trachomatis culture by tympanocentesis or myringotomy in 26 children and acute otitis media (AOM) or persistent otitis media with effusion (POME). The study population included 12 patients with AOM and 14 patients with POME. C. trachomatis was recovered from the middle ear fluid of two patients (16%) with AOM and from one patient (7%) with POME. Sixty external auditory canal specimens from 30 normal children were cultured. None was positive for C. trachomatis. Because our study population was small the true significance of this organism as a pathogen in ADM or POME is impossible to assess at this time.

Acute Disease↗
PubMedDate not supplied

Modulation of biological processes by mineral fiber adsorption of macromolecules in vitro.

Three classes of macromolecules (i.e., DNA, RNA, and protein) were shown to be adsorbed to asbestiform minerals. The cytotoxicity exerted by the fibers on a normal human fibroblast cell line, which may be an indicator of the carcinogenic potential of mineral fibers, correlated positively with the degree of macromolecular adsorption of the fiber, namely: chrysotile greater than amosite greater than glass fiber. Asbestiform fibers also induce an alteration in in vitro DNA hydrolysis by bovine pancreatic deoxyribonuclease. This phenomenon suggests that adsorption by asbestiform minerals may modulate biological processes by inducing a conformational change in biological macromolecules as a result of coulombic interaction between the surface charge of the fiber and the hydrophilic groups on the macromolecule.

Adsorption↗
PubMedDate not supplied

Antepartum diagnosis and management of idiopathic pericardial and pleural effusion: report of one case.

A case of an antenatal ultrasound diagnosis of pericardial effusion with pleural effusion is reported. Fetal pericardiocentesis, thoracentesis and amniocentesis were performed with real-time ultrasound guidance at 37 weeks of gestation. Laboratory investigations reported a rhesus-positive blood group, no atypical antibodies, negative serologic test for syphilis, and negative titers for toxoplasmosis. The laboratory data of the pericardial effusion showed: glucose 71 mg/dl, protein 3.7 gm/dl, LDH 73 U/L, CPK 53 U/L, negative culture for virus and bacteria. The pregnancy was terminated at 37 weeks of gestation by Cesarean section because of an edematously enlarged thorax. A 3540 gm male infant was delivered in a state of asphyxia with general cyanosis and an Apgar score of 3 and 4 at one and five minutes, respectively. His condition improved after endotracheal intubation and assisted ventilation. He was transported to the neonate intensive care unit, where chest roentgenogram confirmed pleural effusion over the left side. Chest tube was placed for 7 days. The infant was discharged on day 8, but the fluid reaccumulation over the left lung four months later. Chest tube was placed for five days. The infant subsequently has thrived with appropriated development for his age. We report herein because of successful technique of antepartal intervention.

Adult↗
PubMedDate not supplied

DNA damage, repair, replication, and tumor incidence in the BDIV rat strain following administration of N-ethyl-N-nitrosourea.

Berlin-Druckrey (BD-IV) rats were used to evaluate the level of neoplastic transformation, initiation of DNA damage and repair following treatment with N-ethyl-N-nitrosourea (ENU). ENU, a potent neurocarcinogen in the Sprague-Dawley (CD) and BDIX rat strains, was a less potent neurocarcinogen when administered to 30 day old BDIV rats. ENU induced significantly higher levels of tumors of the nervous system, kidney, and liver in CD rats than in BDIV rats. Initial DNA damage was determined by quantitating and comparing the number of alkaline labile sites (ALS) and alkylation of [14C]ENU to deoxyguanosine in the brain, kidney, and liver of BDIV rats. A smaller percentage of ALS were lost from the DNA of the brain (10-15%) than from the kidney (19-27%) and liver (30%). Similarly, loss of 0(6)-ethylguanine was greatest in liver (100%), next in kidney (73%), and least in brain (23%) DNA during a seven-day period. Loss of N7-ethylguanine ranged between 23-44%. These levels of repair are similar to those previously observed in the more sensitive Sprague-Dawley rat. Cellular replication was highest in the liver and lowest in the brain of BDIV rats at 30 days of age and was inhibited to varying extents in all three tissues by ENU. These data indicate, that while there is a good correlation between organ sensitivity to ENU induced carcinogenesis and the persistence of DNA lesions and levels of DNA replication in the same strain of rat, there is no correlation across strains with different carcinogenic potential.

Animals↗