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Biomedical subjects

J C Chang

Publications and source records attributed to J C Chang.

At least 217 records · Page 12Linked to original sources

Nasal cavity deposition, histopathology, and cell proliferation after single or repeated formaldehyde exposures in B6C3F1 mice and F-344 rats.

Inhalation exposure for 2 years to 14.3 ppm formaldehyde (HCHO) induced a 50% incidence of squamous cell carcinoma in the nasal cavity of F-344 rats but only a 3.3% incidence in B6C3F1 mice. Since the response was concentration and species dependent, species differences in nasal cavity "dose" were examined as a possible mechanism for the differences in tumor incidence. Naive (nonpretreated) and HCHO-pretreated (6 or 15 ppm, 6 hr/day, 4 days) mice and rats were exposed to HCHO for 6 hr during which respiratory rate and tidal volume were recorded to calculate the theoretical deposition (micrograms/min/cm2) of HCHO on the nasal epithelium. Species differences in delivered "dose" were further assessed by comparative autoradiography, histopathology, and cell turnover studies. Because mice were better able to reduce minute ventilation upon repeated exposures, they had less HCHO available for deposition than rats, resulting in less tissue damage and a lower rate of cell turnover in the nasal epithelium. The correlation between calculated "dose" and observed nasal toxicity, including nasal tumor incidence, demonstrates that by normalizing the dosimetry to nasal surface area, species differences in nasal toxicity may be better understood.

Animals↗

Sulfhydryl oxidation in rat nasal mucosal tissues after chlorine inhalation.

Male F-344 rats were exposed to target concentrations of 2.5, 5, or 10 ppm Cl2 for various amounts of time, after which respiratory and olfactory nasal mucosal tissues were analyzed for changes in total sulfhydryl (TSH) content. No changes in olfactory mucosa TSH content were observed at the maximum Cl2 exposure. Decreases in content of respiratory mucosa TSH were seen after 6 hr exposures to 5 ppm and 10 ppm, but not 2.5 ppm. The concentration of TSH returned to control values 19 hr after termination of exposure. Analysis of TSH changes in concentration X time (CT) studies suggested that decreases in TSH were dependent on the airborne concentration of Cl2 and not on 'dose' (the CT product). The results suggest that inhaled Cl2 can oxidize tissue sulfhydryl groups at the point of entry, but not at deeper regions of the respiratory tract.

Administration, Intranasal↗

Bronchioalveolar carcinoma arising in areas previously irradiated for Hodgkin's disease.

A man who received therapeutic irradiation to limited areas of each lung for intrapulmonary Hodgkin's disease developed bronchioalveolar carcinoma in the same areas more than 20 years later. This is the first report of a malignant process developing in areas of the lung that had been previously irradiated for treatment of a primary lung condition.

Adenocarcinoma, Bronchiolo-Alveolar↗

Cathepsin B and prolyl endopeptidase activity in rat peritoneal and alveolar macrophages. Stimulation of peritoneal macrophages by saline lavage.

Cathepsin B and prolyl endopeptidase activity was determined in purified rat pulmonary and peritoneal macrophages and cathepsin B was determined in blood monocytes. The activity of cathepsin B in pulmonary macrophages was more than two times higher than in resident peritoneal macrophages and about eight times higher than in circulating monocytes. The simple process of peritoneal lavage with PBS induced an increase in cathepsin B activity in peritoneal macrophages that by 96 and 144 hr reached those levels observed in pulmonary macrophages. Both pulmonary and peritoneal macrophages contain prolyl endopeptidase activity. Repeated peritoneal lavage induced a significant increase in the activity of the enzyme, but not of the magnitude observed for cathepsin B. The data suggest that the transformation of monocytes into macrophages is associated with a significant increase in cathepsin B activity and that this increase is much greater in pulmonary than in peritoneal macrophages.

Animals↗

Muscular pseudotumor of the breast following doxorubicin and radiation therapy for oat cell carcinoma of the lung.

Two male patients developed muscular pseudotumor of the breast following combined treatment of radiation and chemotherapy with cyclophosphamide, doxorubicin, methotrexate and procarbazine for oat cell carcinoma of the lung. The pathologic findings of the biopsy specimens revealed muscle and capillary changes similar to previously reported myocardiotoxicity from doxorubicin and radiation therapy. Discussed is a possible additive or synergistic toxic effect of doxorubicin and radiation therapy in the development of muscular pseudotumor of the breast.

Breast Neoplasms↗

Assigning the polymorphic human insulin gene to the short arm of chromosome 11 by chromosome sorting.

We have determined the subchromosomal location of the human insulin gene by analyzing DNA isolated from sorted human metaphase chromosomes. Metaphase chromosome suspensions were sorted into fractions according to relative Hoechst fluorescence intensity by the fluorescence activated chromosome sorter. The chromosomal DNA in each fraction was characterized by restriction endonuclease analysis. Initial sorts indicated that the insulin gene-containing fragment resided in a fraction containing chromosomes 9, 10, 11, and 12. Studies of cell lines that contained chromosome translocations permitted the assignment of the insulin gene to a derivative chromosome that contains portions of the short arm of chromosome II. Simultaneous sorting of the normal homolog from this small derivative chromosome separated the two different sized insulin gene-containing restriction fragments in this individual. These data indicate that the two restriction fragments represent insulin gene polymorphism and not duplicate gene loci.

Alleles↗

Prognostic significance of surgical perforation of the rectum during abdominoperineal resection for rectal carcinoma.

Two hundred fifty patients were followed up after resection for carcinoma of the rectum. Sixty-four (25.6 percent) had a surgical perforation in the resected rectum. Perforation did not affect the long term outcome in patients with Dukes' A or D tumors, but in patients with Dukes' B and C cancers the surgical defect was associated with an increased incidence of recurrent tumor (57 versus 34 percent) and a decreased 5 year survival rate (31 versus 46 percent). The local recurrence rate was significantly higher in patients with Dukes' B rectal cancer who had an iatrogenic perforation (25.9 percent) than in those without a perforation (8.1 percent). This increased local recurrence rate was as high as the local recurrence rate in patients with Dukes' C cancers (23 percent) with or without a perforation. Patients with Dukes' B or C cancers who had incomplete resection had survival patterns similar to those in patients with Dukes' D cancers. Failure to remove all gross tumor and failure to avoid rectal perforation during abdominoperineal resection increases the risk of recurrence and decreases the chance of long-term survival.

Female↗

A sensitive test for prenatal diagnosis of sickle cell anemia: direct analysis of amniocyte DNA with MstII.

The restriction endonuclease MstII cleaves the human beta-globin gene at the position corresponding to amino acids 5, 6, and 7. The beta S mutation at this position abolishes the recognition site. Hence, the two normal DNA fragments in this region, 1.15 and 0.2 kb in length, are replaced by a single 1.35-kb fragment in DNA from sickle cell anemia. We have set up an assay using these findings. The assay is extremely sensitive and can be applied to DNA directly harvested from 20 ml of amniotic fluid.

Amniotic Fluid↗

Correlation of estrogen receptors and response to chemotherapy of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in advanced breast cancer.

Thirty-six patients with advanced breast cancer were treated with the regimen of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). Their response to the combination chemotherapy and their survival were correlated in respect to estrogen-receptor (ER) status. No patient had received any form of hormonal therapy or other chemotherapeutic agents prior to the CMF treatment. Overall response rate, both complete and partial, to chemotherapy was 60% (21/36): 88% in the ER+ group and seven months in the ER--. Median duration of survival was 27 months in ER+ patients and nine months in ER-- patients after initiation of chemotherapy. These data suggest ER+ status has a beneficial effect in the responsiveness of advanced breast cancer to CMF chemotherapy and is prognostic of better survival.

Breast Neoplasms↗

Antenatal diagnosis of sickle cell anaemia by direct analysis of the sickle mutation.

Sickle cell anemia was detected antenatally by restriction analysis with the enzyme Dde I, which cleaves normal human DNA at the position corresponding to aminoacid number 6 of the beta-globin chain. This site is abolished by the mutation in sickle cell disease, and hence different-sized fragments are generated on digestion of normal and sickle genes with this enzyme. In a pregnancy at risk for sickle cell anaemia, digestion of DNA from cultured amniotic fluid cells revealed a pattern indicating the haemoglobin AA genotype. The diagnosis was later confirmed by fetal blood analysis. The test proved applicable to the sickle gene from Africa, Asia, The Middle East, and two Mediterranean countries.

Amniocentesis↗

beta zero thalassemia in Sardinia is caused by a nonsense mutation.

We report the characterization of a molecular lesion of beta thalassemia in Sardinia. Beta thalassemia in this area is predominantly the beta zero type with low levels of beta-globin mRNA. Translation assay of this messenger RNA in a cell-free system showed beta-globin chain synthesis only with the addition of an amber (UAG) suppressor transfer RNA. Double-stranded complementary DNA prepared from reticulocyte mRNA from a Sardinian patient was cloned in a bacterial plasmid and a beta-globin complementary DNA containing clone was isolated and sequenced. At the position corresponding to amino acid number 39, a single nucleotide mutation converted a glutamine codon (CAG) to an amber termination codon (UAG). We previously reported an amber nonsense mutation at amino acid 17 as a cause of Chinese beta zero thalassemia. Thus, beta zero thalassemia in Sardinia represents the second example of a nonsense mutation, and we predict that other beta zero thalassemias with mutations at various points along the beta-globin chain will be found to form a discrete subgroup of beta zero thalassemia. These experiments further illustrate the heterogeneity of lesions that lead to defective globin chain synthesis in beta thalassemia.

Bacteriophage lambda↗