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Biomedical subjects

C C Brown

Publications and source records attributed to C C Brown.

At least 109 records · Page 6Linked to original sources
PubMed1989

Additive and multiplicative models and multistage carcinogenesis theory.

In light of the Armitage-Doll multistage carcinogenesis theory, this paper examines the assumption that an additive relative risk relationship is indicative of two carcinogens that affect the same stage in the cancer process. We present formulas to compute excess cancer risks for a variety of patterns for limited exposure durations to two carcinogens that affect the first and penultimate stages; and using an index of synergy proposed by Thomas (1982), we find a number of these patterns to produce additive, or nearly additive, relative risk relationships. The consistent feature of these patterns is that the two exposure periods are of short duration and occur close together.

Carcinogens, Environmental↗
PubMed1989

Equine zygomycosis caused by Conidiobolus lamprauges.

A 15-year-old Arabian mare from southern Louisiana with a 2-month history of periodic epistaxis and severe weight loss had a large, fibrosing, granulomatous mass containing numerous nodules ("kunkers") projecting dorsally into the nasopharynx, and was euthanized at the owner's request. In addition to these kunkers, the mass contained a single trematode tentatively identified as Fasciola hepatica. Several kunkers were removed, washed thoroughly in sterile water and embedded in nutrient agars; the fungus that grew out of them was identified as Conidiobolus lamprauges Drechsler (Entomophthorales: Ancylistaceae). This is the first report of C. lamprauges from any vertebrate mycosis, and only the third Conidiobolus species reported from vertebrates. Unlike many other entomophthoraleans, the fungus isolated from this mycosis grew well at 37 degrees C. The possible means by which Conidiobolus species may infect vertebrates is discussed. These mycoses probably result most often from chronic exposure during sleep to conidia discharged from fungal growth on decaying plant material in the bedding.

Animals↗
PubMed1989

Use of in situ hybridization for the detection of foot-and-mouth disease virus in cell culture.

Biotinylated complementary DNA (cDNA) and RNA probes were prepared from a specific and highly conserved section of the foot-and-mouth disease virus (FMDV) genome coding for the RNA-dependent RNA polymerase. Hybridization was conducted on FMDV-infected, bovine enterovirus (BEV)-infected, and noninfected swine kidney cell cultures. The detection system utilized the enzyme system streptavidin-alkaline phosphatase, the substrate phosphate, and the chromogen nitroblue tetrazolium. Intense cytoplasmic granular staining was present at 2 and 4 hr postinfection (hpi), with less staining observed at 24 hpi. The staining was specific for FMDV, as indicated by a lack of staining of noninfected cells and BEV-infected cells. With the RNA probe, positive cells were detected up to the highest viral dilution assayed, which was approximately 96 TCID50. The cDNA probe was slightly less sensitive, detecting positive cells at 10-fold lower dilutions. This technique could prove useful in the diagnosis of foot-and-mouth disease in animals or in the detection of FMDV in biologics submitted for importation.

Animals↗
PubMed1989

Immunolocalization of metalloproteinases and their inhibitor in the rabbit growth plate.

UNLABELLED: The synthesis and distribution of three metalloproteinases, collagenase, stromelysin, and gelatinase, and of the tissue inhibitor of metalloproteinase were examined in the distal femoral growth plate, the secondary center of ossification, and the perichondral ossification groove of Ranvier in newborn to six-week-old rabbits. Specific antisera to each of the enzymes and to the tissue inhibitor of metalloproteinase were used to identify their distribution in the extracellular matrix of the growth plate and to determine the associated tissues and cells that are responsible for their synthesis. Immunolocalization using tissue that was cultured in the presence of monensin to augment accumulation of intracellular antigen revealed that the growth-plate chondrocyte is responsible for the synthesis of the metalloproteinases and the tissue inhibitor of metalloproteinase, and that there is a unique pattern of synthesis in each zone. Chondrocytes of the resting and proximal proliferative zones were shown to synthesize and secrete all of the metalloproteinases and the tissue inhibitor of metalloproteinase. Synthesis of collagenase also was demonstrated in the remainder of the proliferative zone and in the most distal cells of the hypertrophic zone. The presence of collagenase in the distal cells suggests their involvement in vascular invasion. By culturing tissues in the presence of antibodies, we were able to demonstrate collagenase and the tissue inhibitor of metalloproteinase throughout the growth-plate matrix. Staining of the extracellular matrix, implying active collagenase, was also found in the matrix of the proliferative and hypertrophic zones, suggesting that degradation of tissue may occur at a distance from the cells that synthesize the enzyme. Simultaneous localization with two different antibodies demonstrated that growth-plate chondrocytes are capable of synthesizing collagenase and the tissue inhibitor of metalloproteinase, both independently of one another and coordinately. Stromelysin was found to be synthesized in all zones, implying that it plays an important role in degradation. Monocyte-conditioned media stimulates synthesis of collagenase in growth-plate cells, principally through the action of interleukin-1. All chondrocytes throughout the growth plate, including hypertrophic cells, can be stimulated to produce collagenase. These changes in metalloproteinase and in the tissue inhibitory of metalloproteinase in the growth plate are crucial to remodelling of the matrix during development, and the appearance of metalloproteinases and the tissue inhibitory of metalloproteinase in the secondary ossification center and groove of Ranvier indicates that changes at these sites are similar to remodeling in the growth plate. CLINICAL RELEVANCE: The life cycle of the chondrocyte in the growth plate is central to the process of endochondral ossification, bone growth, and development. Our new data on the zonal synthesis of metalloproteinase and of th

Animals↗
PubMed1989

An evaluation of uterine scar integrity after cesarean section in rabbits.

Cesarean sections were performed on 30 rabbits at term pregnancy. Two incisions were made in each of the two uterine horns, and each incision was closed according to a predetermined method (continuous, everted; continuous, inverted; interrupted, everted; or interrupted, inverted). Tissue from the uterine scar region was sampled at three different time periods (5-8 days, 12-15 days, or 28-30 days) post-surgery to evaluate the degree of uterine healing by a variety of histologic criteria. The initial healing response in the scarred region occurred around 28-30 days post-surgery. The different uterine closure techniques did not appreciably influence the healing response in this study. We evaluated tensile strength in 36 uterine muscle specimens containing the scar obtained from nine animals in the 28-32-days post-surgery group. Of these 36 specimens, 86.1% tore through the muscle instead of through the scar when tension was applied to the muscle.

Animals↗
PubMed1988

Projections of lung cancer mortality in the United States: 1985-2025.

Lung cancer has been the leading cause of cancer death in the United States for the larger part of this century. Increases in smoking prevalence from the 1900s through the 1950s have resulted in more than 100,000 deaths annually. Because of the changes during the last three decades in smoking prevalence, the decreasing tar content of cigarettes, and the increasing popularity of low-tar cigarettes, trends in lung cancer are difficult to predict. This article presents an analysis of smoking and lung cancer data using an age-period-cohort model for projecting lung cancer mortality through the year 2025. The projections are based on the initial parameterization of the model and on prevention objectives related to smoking behavior established by the National Cancer Institute. It is concluded that the recent trends in lung cancer are unlikely to be affected by changes in cigarette composition and consumption in the near term, but increasing the effectiveness of anti-smoking campaigns can have a considerable effect on lung cancer rates in the more distant future.

Adult↗
PubMed1988

Retinoic acids promote the repair of the dermal damage and the effacement of wrinkles in the UVB-irradiated hairless mouse.

Chronic irradiation of hairless mice with UVB leads to elastosis as evidenced by both histologic means and an increase in skin desmosine content. Treatment with topical all-trans- or 13-cis-retinoic acid causes dose-dependent increments in the area of the dermal "repair zone"; skin desmosine content increases during irradiation but does not change significantly after irradiation is discontinued and retinoic acid treatment commenced. During the course of the irradiation the animals develop permanent wrinkles on the exposed dorsal surface, which can be recorded in plastic impressions. The extent of wrinkling can be quantitated and it has been demonstrated that topically applied retinoic acids lead to the complete effacement of these surface features and that the process appears to be permanent.

Aging↗
PubMed1988

Endogenous lipid pneumonia in opossums from Louisiana.

Endogenous lipid pneumonia was present in 19 of 27 opossums (Didelphis virginiana) trapped in the vicinity of Baton Rouge, Louisiana. The severity of lesions varied from small pleural and subpleural aggregates of foamy macrophages with minimal disruption of pulmonary architecture to large nodular accumulations of foam cells with cholesterol clefts and localized emphysema. The cause of the lipid pneumonia may be related to pulmonary nematode parasite infections, which were evident in 13 of the affected animals.

Animals↗
PubMed1988

Use of immunohistochemical methods for diagnosis of equine pythiosis.

Excisional biopsy specimens were received from 8 horses with lesions suspected of being caused by Pythium sp. Pythium sp was isolated from all specimens. An indirect peroxidase technique was applied to formalin-fixed tissues from the biopsy material and there was distinct staining of hyphal cell walls in all specimens. Sections containing hyphae, other than those of Pythium sp, failed to stain. The indirect peroxidase technique could be used for confirmation of suspected cases of pythiosis.

Animals↗
PubMed1988

Chemotactic disorders.

Clinical disorders of phagocyte chemotaxis have heterogeneous etiologies. The physiologic defect can involve adherence, the cytoskeleton, deformability, granule dysfunction, regulation of receptors, or a variety of soluble mediators. At present, successful clinical management depends on early and compulsive attention to infectious complications. A host of new immunomodulators (GM-CSF, gamma interferon, tumor necrosis factor, etc.), made available through recombinant gene technology, are now under study and may provide new and more effective means of treatment for these life-threatening disorders.

Chemotactic Factors↗
PubMed1987

Use of multistage models to infer stage affected by carcinogenic exposure: example of lung cancer and cigarette smoking.

Statistical methods based on the Armitage-Doll mathematical model of the carcinogenic process are presented for analyzing epidemiologic case-control studies of cancer. These methods are proposed to provide inferences regarding the stage(s) in the cancer process at which the exposure of interest acts. An example of these methods is given which shows evidence that carcinogens in cigarette smoke appear to affect the transition rates for two separate stages in the development of lung cancer, and the relative magnitudes of these effects are estimated. The data for this analysis came from a European multi-center case-control study of lung cancer. The results of the analysis show that: (1) the relative risk of lung cancer among continuing smokers compared to nonsmokers of the same age decreases as the age started smoking increases, while the rate of smoking stays fixed, a result which indicates a carcinogenic effect on an early stage in the process; and (2) the relative risk among ex-smokers compared to continuing smokers having the same duration and rate of smoking decreases with time since smoking stopped, a result which indicates a carcinogenic effect on a late stage in the process. Both results are shown to be best described by the hypothesis that cigarette smoking affects two stages. The estimated relative magnitudes of cigarettes' carcinogenic effects on the two stages indicate that the largest proportion of the total lifetime lung cancer risk among continuing smokers is due to its late stage effect, and that the proportion of risk due to causes other than smoking varies from 23% among men smoking 1-10 cigarettes per day to 6% among those smoking greater than 30 cigarettes per day. These findings imply that preventive measures directed toward inducing smokers to stop would have a potentially substantial payoff in reducing future lung cancer mortality.

Age Factors↗
PubMed1987

Effect of heparin on synthesis of short chain collagen by chondrocytes and smooth muscle cells.

The treatment of embryonic chick chondrocyte cultures with heparin results in a decrease in collagen synthesis. One of the collagens synthesized by hypertrophic chondrocytes, specifically type X collagen, may play an important role in cartilage mineralization and endochondral ossification. Recently a new short chain collagenous component was found in cultures of rat vascular smooth muscle cells (Majack, R. A., and P. Bornstein, 1985, J. Cell Biol., 100: 613-619). The present study was initiated to investigate heparin's effect on type X collagen in embryonic chick chondrocytes and to further evaluate the nature of the short chain component synthesized by rat vascular smooth muscle cells. Different tissues may respond differently to the administration of heparin. In chondrocyte cultures heparin decreased both total collagen synthesis as well as the synthesis of type X collagen. There was an accumulation of collagen precursors, found principally in the cell layer compartment, which appeared to be the result of heparin's inhibition of the NH2-terminal protease. In cultures of rat vascular smooth muscle cells heparin was found to increase the synthesis of a short chain collagenous component as previously reported. However, comparison with a type X collagen standard showed this to be different from type X. In all cases, the effect of heparin on collagen chain precursors, chondrocyte type X synthesis, and synthesis of a vascular smooth muscle short chain collagen was shown to be reversible. Similar effects were obtained by adding chondroitin sulfate to chondrocytes, suggesting a role for extracellular matrix components in the modulation of collagen synthesis. These findings are consistent with the concept of a group of short chain collagens with type X collagen being unique to hypertrophic chondrocytes.

Animals↗
PubMed1987

Biologically motivated cancer risk models.

A two-stage dose response model is proposed for use in cancer risk assessment. The model assumes that transformation probabilities and cellular dynamics are exposure- and time-dependent.

Animals↗
PubMed1987

Differentiating among proposed mechanisms for tumor promotion in mouse skin with the use of the multievent model for cancer.

Numerous mechanisms for tumor promotion in mouse skin have been recently proposed. These include the multistage, genetic view of Slaga, Furstenberger, and Marks; the multistage, genetic and/or epigenetic view of Parkinson; and the two-stage view of Yuspa and Hennings. With the use of the multievent model, a mathematical model for cancer that can incorporate cell proliferation phenomena, these tumor promotion mechanisms were modeled mathematically. It was found that the models had different predictions about the incidence of papillomas in initiator-promoter-initiator experiments and the incidence of carcinomas in initiator-promoter experiments with varying periods of tumor promotion. Upon analysis, existing data were shown to be in agreement with the Yuspa and Hennings two-stage model. The analysis also supported the view, formulated by Scribner and co-workers, that different types of initiated cells were created, some capable of transformation to carcinomas and some not. Phenomena determined by use of benign tumors as the end point may need to be demonstrated with the use of the carcinoma as the end point, prior to the acceptance of these phenomena being applicable to the human carcinogenic process.

4-Nitroquinoline-1-oxide↗
PubMed1987

Cancer incidence and mortality trends among whites in the United States, 1947-84.

Cancer incidence trends from the late 1940s to 1983-84 were assessed among white residents of five geographic areas (Atlanta, Connecticut, Detroit, Iowa, San Francisco-Oakland) by means of data derived from several National Cancer Institute surveys, the Connecticut Tumor Registry, and the Surveillance, Epidemiology, and End Results Program. Incidence trends were compared with mortality trends for the entire United States and for the same five study areas. This study documented rising incidence and mortality rates for four cancers: lung cancer, melanoma of the skin, multiple myeloma, and non-Hodgkin's lymphomas. Increases in lung cancer continued through the early 1980s, but the rate of increase has been moderating during recent years, particularly among males and at younger ages for whom recent declines are evident. Overall, lung cancer incidence rates increased more than 220 and 400% among males and females, respectively. Although much rarer than lung cancer, melanoma of the skin and multiple myeloma increased greatly until the early 1980s among both males and females. The overall rate of increase in melanoma incidence among males was greater than that for lung cancer, and the rate of increase in multiple myeloma mortality among females was exceeded only by that for lung cancer. Increases of 70-120% were observed for non-Hodgkin's lymphomas. Increases in incidence and mortality rates for pancreatic cancer were apparent during the early years but less conspicuous in recent years. Laryngeal and kidney cancer rates generally increased substantially, although the changes were not remarkable for laryngeal cancer mortality among males and kidney cancer mortality among females. The rates for cancers of the mouth and pharynx increased among females but not males. Prostate, colon, and bladder cancer incidence rates increased more than 65% among males, whereas mortality rates changed only moderately. The incidence of thyroid cancer increased more than 75% among both sexes until the late 1970s, but mortality rates have declined during the period of study. Breast cancer incidence increased 30%, whereas mortality rates remained remarkably constant. The incidence of corpus uteri cancer increased dramatically during the mid-1970s and decreased substantially thereafter; these changes were not reflected in the mortality rates, which continually declined during the entire time period. The incidence of testicular cancer increased more than 90% and that of Hodgkin's disease did not change greatly; however, mortality rates for both cancers declined more than 50% since the late 1960s and early 1970s.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Synergistic hemolysis-inhibition titers associated with caseous lymphadenitis in a slaughterhouse survey of goats and sheep in Northeastern Brazil.

A survey of caseous lymphadenitis was conducted at a goat and sheep slaughterhouse in Northeastern Brazil One hundred and fifty-eight goats and 43 sheep were examined for the presence of abscesses, with bacterial culturing of purulent material to define the etiological agent. Blood was collected simultaneously for determination of serological titer via the synergistic hemolysis-inhibition test which measures antibodies to an exotoxin of Corynebacterium pseudotuberculosis. Thirteen and nine-tenths percent of the goats had abscesses, with a high proportion having mediastinal or pulmonary lesions (9.5%). Two sheep had abscesses, both with internal organ involvement. Corynebacterium pseudotuberculosis was the most frequently isolated organism. Of 22 goats with abscesses, 20 were positive via the synergistic hemolysis-inhibition test. Both of the sheep with abscesses had positive synergistic hemolysis-inhibition titers. The proportion of serological reactors was greater than the proportion of animals with abscesses. The synergistic hemolysis-inhibition test may be detecting subclinically infected animals.

Abattoirs↗