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Biomedical subjects

C C Harris

Publications and source records attributed to C C Harris.

At least 343 records · Page 19Linked to original sources
PubMed1984

Interindividual variation in carcinogen metabolism, DNA damage and DNA repair.

A number of laboratory approaches are currently available to measure interindividual variation in carcinogen metabolism, amounts of carcinogen-DNA adducts and DNA repair capacity. Wide interindividual variations have been found among strains of experimental inbred animals and among individuals in outbred populations, including humans. The quantitative relationships, if any, between these parameters and the human cancer risk will be determined by biochemical and molecular epidemiological studies, of high and low cancer risk populations and of cancer-prone families.

Animals↗
PubMed1984

Improved SPECT quantification using compensation for scattered photons.

SPECT images are degraded by the inclusion of Compton-scattered photons within the pulse-height window. Phantom and patient studies with Tc-99m were used to evaluate a compensation method that consists of subtracting a fraction of the image reconstructed using events recorded within a secondary pulse-height window (92-125 keV) from that derived from the photopeak pulse-height window (127-153 keV). Images of line sources in air and in a water-filled phantom were stored. The compensated line spread functions (LSFs) were evaluated. In water, the absolute counting rates for the SPECT LSFs were within 10% of the rates measured in air. The phantom consisted of six solid acrylic spheres (diameters 10, 13, 16, 19, 25, 32 mm) placed within a cylindrical (22 cm diam) distribution of Tc-99m. For sphere diameters greater than 25 mm, the measured image contrasts were within 8% of the true uptake ratios. Our results have shown that high-quality, camera-based SPECT systems can reconstruct artifact-free images by making additional use of projection data acquired in a pulse-height window other than that over the primary photopeak. This compensation method results in qualitative and quantitative improvements for the limited source geometries investigated. Further studies are required to optimize this heuristic approach for other source geometries.

Humans↗
PubMed1984

O6-alkylguanine-DNA alkyltransferase activity in normal human tissues and cells.

Normal adult human tissues and cultured bronchial epithelial cells and fibroblasts exhibit O6-alkylguanine-DNA alkyltransferase activity in vitro by catalyzing the repair of the promutagenic alkylation lesion O6-methylguanine from DNA. The amount repaired by extracts of liver, peripheral lung, and colon extracts was proportional to the amount of extract protein. Repair of O6-methylguanine led to stoichiometric regeneration of guanine in the DNA and stoichiometric formation of S-methylcysteine in protein. Alkyltransferase activity varies in the different human tissues tested in the decreasing order of liver greater than colon greater than esophagus greater than peripheral lung greater than brain. Extracts of lung tissues, cultured human bronchial epithelial cells, and fibroblasts had similar alkyltransferase activities. Various human tissues exhibit 2- to 10-fold higher alkyltransferase activity than corresponding rat tissues. Whereas the interindividual variation of the activity was 4- to 5-fold in ten or more human lung and colon specimens, the interindividual variation in the inbred rat was less than 20%. The present results show that different human tissues and cells have a several-fold higher capacity to repair O6-methylguanine in DNA than do rat tissues and that the repair process occurs via a mechanism similar to that shown previously in other mammalian cells and Escherichia coli.

Adult↗
PubMed1983

High-frequency transfection and cytopathology of the hepatitis B virus core antigen gene in human cells.

A protoplast fusion method was developed to stably transfect human cells with pSV2-derived plasmids at frequencies greater than 10(-3). This procedure made it possible to test the biological effect of a hepatitis B virus (HBV) gene independent of the viral structures required for infection. A pSV2gpt+ plasmid constructed to carry a subgenomic fragment of HBV that contained the core antigen gene (HBc gene) was transfected into human cells. A human epithelial cell line was stably transfected with the HBc+ gene by selecting recipient cells for expression of guanine phosphoribosyl transferase expression. With this gpt+/HBc+ cell line it was shown that growth in serum-free medium or treatment with 5'-azacytidine stimulates the production of the HBV core antigen. A hepatocellular carcinoma carrying the entire HBV genome was stimulated to produce the HBc gene product in response to the same factors that stimulated HBcAg production in the gpt+/HBc+ cell line constructed by transfection. The temporal relation between the cytopathologic response and HBc gene expression was similar for both cell types, indicating a primary role for HBc gene expression in the cytopathology of HBV-infected human liver.

Azacitidine↗
PubMed1983

Formaldehyde damage to DNA and inhibition of DNA repair in human bronchial cells.

Cultured bronchial epithelial and fibroblastic cells from humans were used to study DNA damage and toxicity caused by formaldehyde. Formaldehyde caused the formation of cross-links between DNA and proteins, caused single-strand breaks in DNA, and inhibited the resealing of single-strand breaks produced by ionizing radiation. Formaldehyde also inhibited the unscheduled DNA synthesis that occurs after exposure of cells to ultraviolet irradiation or to benzo[a]pyrene diolexpoxide but at doses substantially higher than those required to inhibit the resealing of x-ray-induced single-strand breaks. Therefore, formaldehyde could exert its mutagenic and carcinogenic effects by both damaging DNA and inhibiting DNA repair.

Bronchi↗
PubMed1983

Tissue-specific expression of keratin proteins in human esophageal and epidermal epithelium and their cultured keratinocytes.

In contrast to the simplified keratin content of bovine, rabbit, and rat esophageal epithelium (composed mainly of a 57 and 46 or 51 kD keratin, depending on the animal species), human esophageal epithelium contained a quantitatively different array of keratin proteins, ranging in molecular weight from 37 to 61 kD. The pattern of keratin proteins from human esophageal epithelium differed qualitatively and quantitatively from that of human epidermis. Human esophageal epithelium lacked the 63, 65, and 67 kD keratins characteristic of human epidermis, consistent with the absence of a granular layer and an anucleate stratum corneum. Moreover, human esophageal epithelium contained a distinctive 61 kD keratin protein which was either not present or present in only small amounts in human epidermis and variable amounts of a 37 kD keratin. Whereas the 56, 59, and 67 kD keratins were the most abundant keratins in human epidermis, the 52, 57, and 61 kD keratins predominated in human esophageal epithelium. During in vitro cultivation, both human epidermal and esophageal keratinocytes produce colonies which are stratified, but the morphologic appearance of these cultured epithelia differs. Only cultured human epidermal keratinocytes contain keratohyalin granules in the outermost layers and a prominent 67 kD keratin on immunoprecipitation. Otherwise the keratin contents appear similar. In conclusion, human esophageal epithelium exhibited intertissue and interspecies differences in the pattern of keratin proteins. During in vitro cultivation, human esophageal keratinocytes retained some aspects of their distinctive program of differentiation.

Animals↗
PubMed1983

Proliferative and cytotoxic effects of Fusarium T2 toxin on cultured human fetal esophagus.

In an area with high incidence of esophageal cancer, Linxian, staple food is heavily contaminated by fungi of the Fusarium genus. We have found that T-2 toxin produced by Fusarium has both direct cytotoxic and proliferative effects on fetal esophageal epithelium. At higher dosage of T-2 toxin (4 ng/ml for 6 days) the cultured epithelium became necrotic. At a lower dosage range of 0.2-1.2 ng/ml, T-2 toxin caused mitogenic effects including focal basal cell hyperplasia, dysplasia, and increased number of mitoses. Atypical mitoses were also seen. These changes are very similar to the premalignant lesions seen in epithelium adjacent to human esophageal carcinoma. These observations suggest that Fusarium mycotoxin can have a role in human esophageal carcinogenesis and should be further investigated.

Cell Division↗
PubMed1983

Artifacts in iodine-131 renal images due to coincidence summing of technetium-99m photons.

Technetium-99m gamma camera images of kidneys produced with an iodine-131 energy window showed "ghosts" over and between the kidneys and between the kidneys and the bladder. The cause was coincidence summing at 281 keV due to a high 99mTc counting rate. In older model cameras careful peaking with a proper energy window reduces this effect; more recently developed cameras with pileup rejection circuits do not have this problem.

Humans↗
PubMed1983

Observations on the intraperitoneal distribution of chromic phosphate (32P) suspension for intraperitoneal therapy.

Seven patients received intraperitoneal chromic phosphate (32P) suspension in a 3-ml bolus with a saline flush, and another ten patients were given the suspension in a 500-ml infusion of normal saline. During the first six hours after administration, most 32P activity redistributed to the gravity-dependent portion of the peritoneal cavity. From 24 hours up to seven weeks after administration, activity distributions were fixed. Dispersions were heterogeneous in every patient, but the most marked examples of localized activity occurred in patients who had received bolus injections. We concluded that large-volume infusions and frequent changes in patient position for several hours following the infusion, contribute to improved dispersion of 32P suspension.

Chromium↗
PubMed1983

The use of a nuclear medicine computer as a multichannel pulse-height analyzer. Design of an interface.

An interface has been designed to acquire energy signals from gamma cameras as one-dimensional images on a nuclear medicine computer. The images are converted to pulse-height spectrum curves with image-profile routines. Several spectra are acquired in a 256 X 256-pixel image; data are analyzed in image or curve modes. The quality of gamma cameras and other detectors can then be assured.

Computers↗
PubMed1983

The radionuclide renogram as a predictor of relative renal blood flow.

Radionuclide renograms obtained with Tc-99m-DTPA were used to calculate relative renal blood flow in 16 dogs. In 13 of these dogs, relative blood flow ratios (R:L) calculated from the renograms were correlated with ratios measured with an electromagnetic flowmeter or with radiolabeled microspheres. The results indicate that Tc-99m-DTPA renograms can be used to make an accurate prediction of relative renal blood flow.

Animals↗
PubMed1983

Metabolism of benzo(a)pyrene and 1-naphthol in cultured human tumorous and nontumorous colon.

The oxidative metabolism of benzo(a)pyrene and the conjugative metabolism of 1-naphthol by explant cultures of normal human colon and colonic tumor tissue, obtained at surgery, have been studied. After 24 hr in culture, the explants were exposed to either [1-14C]-1-naphthol (20 to 100 microM) or [3H]-benzo(a) pyrene (1.5 microM) for a further 1.5 to 24 hr. Both normal-appearing tissue and tumor tissue metabolized benzo(a)pyrene to a wide variety of organic solvent-soluble metabolites, including monohydroxybenzo(a)pyrenes, dihydrodiols, and tetrols. 1-Naphthol was metabolized by cultured human colonic mucosa and tumor tissue to both its glucuronic acid and sulfate ester conjugates. In the normal tissues, with naphthol (20 microM), sulfate ester conjugation predominated. However, with the tumor tissue, sulfate ester conjugation decreased; thus, the percentage of glucuronic acid conjugates, expressed as a percentage of total metabolites formed, was increased significantly compared to normal tissue. The relationship, if any, of these changes to neoplastic transformation is unclear. The technique of explant culture described in this study may be of use for the study of other facets of the pathobiology of solid tumors.

Adenocarcinoma↗
PubMed1983

Improved enzyme immunoassays using biotin-avidin-enzyme complex.

Using the characteristic of a high-affinity complex between enzyme-conjugated avidin and biotin, we improved the techniques of enzyme-linked immunosorbent assay and ultrasensitive enzymatic radioimmunoassay. The method included biotinylation of a specific antibody, complexing of a biotinylated antibody with avidin-alkaline phosphatase conjugate, and addition of the antibody-conjugate complex (with or without a standard amount of antigen for competitive or noncompetitive assays, respectively) to the microtiter wells containing antigen in the solid phase. Once biotinylated, antibodies could be stored for several months. Complexing of biotinylated antibody with avidin-alkaline phosphatase conjugate could also be performed once, and the stock solution could be used for several days. Thus, the steps of enzyme immunoassays were reduced to the addition of only antibody-conjugate complex and enzyme substrate. The improved assays, biotin-avidin-linked enzyme immunoassay and biotin-avidin-linked ultrasensitive radioimmunoassay, were simpler, quicker, less expensive, and more sensitive than their standard counterparts.

Alkaline Phosphatase↗
PubMed1983

Differential control by platelet factors of squamous differentiation in normal and malignant human bronchial epithelial cells.

Recently, we developed a nutritionally optimal medium for rapid clonal growth (greater than 1 population doubling/day) of normal human bronchial epithelial (NHBE) cells. Adding fetal bovine or adult human blood-derived serum to this medium depresses the clonal growth rate of NHBE cells in a dose-dependent fashion. In contrast, 10 representative lines of human lung carcinomas either replicate poorly or fail to grow at all when inoculated at clonal density in serum-free medium, and their rates of multiplication increase in direct proportion to the amount of blood-divided serum added to the optimized medium. Thus, the growth factor requirements of these lung carcinoma cell lines are significantly different from those of their normal counterparts. Blood-divided serum reduces the clonal growth rate of NHBE cells by specifically inducing the normal cells, but not lung carcinoma cells, to undergo squamous differentiation. The differentiation-inducing activity was found in platelet lysates. In addition, a growth-inhibiting activity that did not induce squamous differentiation of NHBE cells was also identified in partially purified commercial preparations of platelet-derived growth factor. This observation was in marked contrast to results using human bronchial fibroblasts and human lung carcinoma cell lines; the growth rate of the former was significantly stimulated by commercial preparations of platelet-derived growth factor, whereas the growth rates of the tumor cell lines were unaffected. These results indicate that an aberration in the cellular differentiation as assayed in vitro is positively correlated with cancer and suggests that decreased responsiveness to inducer(s) of differentiation may be a major aspect of bronchial cell carcinogenesis.

Bronchi↗