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Biomedical subjects

C C Brown

Publications and source records attributed to C C Brown.

At least 19 recordsLinked to original sources

CD34+ bone marrow cells are infected with HIV in a subset of seropositive individuals.

Individuals infected with HIV frequently develop cytopenias and suppressed hematopoiesis. The role of direct HIV infection of hematopoietic progenitor cells in this process has not been defined. In this study, purified CD34+ bone marrow progenitor cells from 74 Zairian and American patients were studied by both coculture viral isolation and polymerase chain reaction for evidence of HIV infection. A total of 36.5% of Zairian and 14% of American patients had HIV infection of the CD34+ cell subset, with as many as 1 in 500 CD34+ cells infected. Most of the Zairian patients in this study had advanced HIV infection and markedly decreased CD4/CD8 T lymphocyte ratios (mean 0.160 +/- 0.08), and no laboratory value predicted the presence of infection in the CD34+ subset of a given Zairian individual. In contrast, American patients with CD34+ cell infection had total CD4 cells less than 20/mm3 and a greater decrease of the CD4/CD8 T lymphocyte ratio compared to seropositive Americans without CD34+ cell infection (p = 0.003). Hematopoiesis, studied by methylcellulose colony assays, was depressed in all seropositive patients studied with no significant further suppression when CD34+ cells were infected. Thus, CD34+ bone marrow progenitor cells are infected in vivo in a subset of seropositive individuals and may serve as an additional reservoir of virus in HIV-infected individuals.

Adult

Quantitative method for comparison of skeletal muscle architectural properties.

A numerical method is presented which calculates the architectural difference index between two muscles. This index is based upon the parameters, identified using statistical discriminant analysis, which best characterize the various muscles. This index can be used to reduce multiple architectural properties into a single value and may be useful in selecting donor muscles which are required to perform a substitute function for another muscle which has been lost or injured.

Animals

A pathogenesis study of highly pathogenic avian influenza virus H5N2 in chickens, using immunohistochemistry.

Eighteen specific pathogen-free chickens (nine hens older than 1 year and nine 15-week-old males) were inoculated with highly pathogenic avian influenza virus A/Chicken/Pennsylvania/1370/1983 (H5N2). Birds were serially killed and tissues collected for histological and immunohistochemical evaluation. In the group of older hens, disease was acute or peracute. By immunohistochemistry, antigen was abundant in capillary endothelium in multiple organs, and staining for antigen in parenchymal cells was marked in brain and heart. In the group of younger male birds, disease was subacute. Immunohistochemical staining of capillary endothelium was less pronounced and viral antigen staining was evident in the parenchymal cells of the heart, brain and kidney.

Animals

Plasma lipid and lipoprotein concentrations of men consuming a low-fat, high-fiber diet.

This study assessed the influence of a low-fat, high-fiber diet on blood lipid concentrations of 42 men with desirable or moderately elevated cholesterol concentrations. A low-fat diet (19% fat, 4% saturated fatty acids, 4.6 g fiber/MJ) was compared with a high-fat diet (41% fat, 15% saturated fatty acids, 2.0 g fiber/MJ) and with subjects' self-selected diets. Substituting the low-fat for the high-fat diet decreased total, low-density-lipoprotein, and high-density-lipoprotein cholesterol by 17-20%. Lipid changes between 6 and 10 wk were minor. A reduction in plasma cholesterol of greater than 0.52 mmol/L was achieved with the low-fat diet in 59% of men changing from their self-selected diets and in 79% changing from the high-fat diet. Percent reduction was independent of subjects' cholesterol classification. Results indicate that significant reductions in plasma cholesterol can be achieved by the majority of men committing to a low-fat, high-fiber diet.

Adult

An epizootic of malignant catarrhal fever in a large captive herd of white-tailed deer (Odocoileus virginianus).

Over a 4-mo period 23 of 28 white-tailed deer kept at a small zoo in New Jersey (USA) died. Clinical signs prior to death were minimal and consisted of depression, central nervous system disorders, and watery diarrhea in a few animals only. Histopathology revealed widespread acute vascular lesions, ranging from modest accumulations of blast-like mononuclear cells and edema in the adventitia through to disruption of the tunica media and thrombosis. These vascular lesions were seen in a variety of organs but were most prominent in lung, heart, liver and intestine. Severe vascular changes were associated with necrosis. Lymphoreticular hyperplasia was evident in the lymphoid tissue of all animals.

Animals

A pathogenesis study of foot-and-mouth disease in cattle, using in situ hybridization.

Eight calves were exposed in an aerosol chamber to nebulized foot-and-mouth disease virus. Two control animals were exposed in a similar manner to cell culture media only. Animals were euthanized at intervals and various tissues examined by in situ hybridization using a biotinylated RNA probe corresponding to a portion of the viral gene coding for the polymerase enzyme. By this technique large amounts of viral nucleic acid were found in coronary band, interdigital cleft and tongue as early as six hours postexposure, indicating a very rapid delivery from the portal of entry to the predilection sites for lesion development. This occurred well before the onset of viremia which by virus isolation was not detectable until 30 hours postexposure. The in situ hybridization signal in these tissues decreased in intensity and extent with time to focally positive areas, occasionally surrounding a vesicle. Other epidermal sites not normally thought of as sites for foot-and-mouth lesion development, such as carpus and eyelid, also had some viral nucleic acid detectable at various time intervals. In the lung by in situ hybridization, alveolar septa had viral nucleic acid early in infection (6-18 h postexposure) while later (36-96 h postexposure), the in situ hybridization signal was prominent in alveolar macrophages.

Animals

Unique human neutrophil populations are defined by monoclonal antibody ED12F8C10.

A mouse IgG1 monoclonal antibody ED12F8C10 (C10) binds a constant percentage of peripheral blood neutrophils in the same individual when studied over time, defining a distinct subset of neutrophils in all normal individuals studied to date. Bone marrow studies confirm that the heterogeneity is present to the same degree at all stages of neutrophil development from the myelocyte to the mature neutrophil. Neither in vivo nor in vitro activation of neutrophils explains or significantly alters the relative percentages of C10-positive and -negative neutrophils in the same individual. With both activation and exudation, however, expression of the C10-defined epitope increases in intensity in the C10 binding subpopulation. Studies of NBT reduction, phagocytosis, adherence, light scattering characteristics, and monoclonal antibody surface binding have failed to demonstrate physical or functional differences between the C10-defined populations. We examined C10 binding in patients with different defects of phagocyte function. In two patients with neutrophil-specific granule deficiency, less than 1% of the neutrophils were found to be C10 positive, while neutrophils from a patient with idiopathic leukemoid reaction and recurrent infections demonstrated greater than 99% C10 binding. Although the present study does not delineate the physiologic significance of C10 binding heterogeneity, it firmly supports the concept of neutrophil heterogeneity at the level of surface antigen expression.

Antibodies, Monoclonal

An immunohistochemical study of the pneumonia caused by peste des petits ruminants virus.

Ten goats were inoculated with peste des petits ruminants virus, a paramyxovirus closely related to rinderpest virus. All goats developed severe clinical disease, 8/10 having coughing or dyspnea as prominent clinical signs. In addition, all of the goats had stomatitis and diarrhea. Histopathologic and immunohistochemical studies were done only on the respiratory tracts. Pathologic changes ranged from mild multifocal bronchiolitis and bronchitis to severe bronchointerstitial pneumonia. Lesions were more severe in anteroventral than caudal lobes. The histologic nature of the viral process in the goat lungs had many features in common with the processes of pneumonia in dogs, due to canine distemper, or pneumonia in human beings, due to measles virus. Immunohistochemical staining of formalin-fixed, paraffin-embedded respiratory tract tissue was performed using an indirect system with rabbit anti-rinderpest virus serum, biotinylated anti-rabbit antibody, streptavidin-alkaline phosphatase, and nitroblue tetrazolium chromogen. Staining was sensitive, highlighting the presence of viral antigen in both lung and trachea of all goats. Viral antigen was found in both cytoplasm and nucleus of tracheal, bronchial, and bronchiolar epithelial cells, type II pneumocytes, syncytial cells, and alveolar macrophages. In general, the amount of staining correlated directly with the severity of the inflammatory process.

Animals

A preliminary study of the pathogenesis of foot-and-mouth disease virus using in situ hybridization.

Five adult guinea pigs were inoculated intraepithelially in the right hindfoot pad with foot-and-mouth disease virus. Animals were euthanatized with carbon dioxide at 4, 10, 24, 48, and 72 hours post-inoculation. Generalized disease developed in the guinea pigs, as evidenced by depression and inappetance by 24 hours post-inoculation and by the formation of vesicles in the noninoculated hindfoot pad by 48 hours post-inoculation. By in situ hybridization, using a 500 base pair biotinylated RNA probe, viral nucleic acid was detected in the noninoculated fore- and hindfoot pads as early as 10 hours post-inoculation, well before any pathologic changes associated with foot-and-mouth disease virus infection were detected. These tissues remained consistently positive for the presence of viral nucleic acid up to the end of the experiment. At this time, in the forefoot pad, even though virus had first been detected with certainty in that tissue 62 hours previously, there was still no microscopic evidence of foot-and-mouth disease virus-induced damage in the histologic section. Similarly, tongue tissue was positive by in situ hybridization at 4, 48, and 72 hours post-inoculation, yet there was never any microscopic evidence of degeneration or vesicle formation. From this preliminary study, it appears that, in the guinea pig, the virus is widely disseminated to foot pads and tongue, with epidermal lesions resulting only in selected areas.

Animals

Pathologic features of dogs inoculated with North American Trypanosoma cruzi isolates.

Twenty-three clinically normal Beagles were inoculated with North American Trypanosoma cruzi isolates from an opossum (Tc-O), an armadillo (Tc-A), or a dog (Tc-D). The dogs were grouped according to the clinical outcome of inoculation. Group 1 consisted of 7 dogs inoculated with Tc-O or Tc-A that died or were euthanatized during acute stages of disease. Group 2 consisted of 5 dogs inoculated with Tc-O or Tc-A, that also developed acute disease, but survived to develop chronic disease. Group 3 consisted of 7 dogs inoculated with Tc-D neither developed acute nor chronic disease. Group 4 consisted of 4 dogs and served as noninoculated controls. In group 1, the gross lesions were diffusely pale myocardiums with right ventricular enlargement, hepatomegaly, and a moderate amount of modified transudate in the abdominal cavity. Severe diffuse granulomatous myocarditis with large numbers of pseudocysts and minimal fibrosis characterized the tissues from all cardiac chambers and septum. The lesions were most severe in the right atrium and ventricle. Mild multifocal myositis and pseudocysts were observed in skeletal muscles and smooth muscles of the urinary bladder and small intestine. Multifocal encephalitis and pseudocysts were in the cerebral cortex, cerebellum, and brain stem. In group 2, the gross lesions were biventricular enlargement and thinning of the ventricular free walls. The right ventricle contained the most severe microscopic changes. There were mild multifocal interstitial lymphohistocytic cellular infiltrates, perivasculitis, and marked fibrosis in all areas of the myocardium. Mild myositis and multifocal encephalitis were seen in the skeletal muscles and brains. Pseudocysts were not observed in any tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

The lesions and prevalence of Trypanosoma cruzi in opossums and armadillos from southern Louisiana.

The prevalence of Trypanosoma cruzi in 48 opossums and 98 armadillos from southern Louisiana was studied. Sixteen opossums (33.3%) and 1 armadillo (1.1%) were positive for T. cruzi by blood culture. Hearts from 45 opossums and the tissues from the 1 blood culture-positive armadillo were available for histopathological examination. Although histopathology revealed T. cruzi pseudocysts in 6 opossums, 2 were not positive on blood culture. Therefore, 18 opossums (37.5%) were positive for T. cruzi. Twenty-two of 45 opossums had histological evidence of myocarditis. No lesion typical of infection with T. cruzi was observed in the armadillo tissues. These results substantiate that the opossum is a current reservoir host of T. cruzi infection in southern Louisiana and that armadillos may be of relatively minor importance.

Animals

Detection of salivary HIV-1-specific IgG antibodies in high-risk populations in Zaire.

Saliva and blood samples were tested for human immunodeficiency virus-1 (HIV-1) antibodies in two high-risk populations in Kinshasa, Zaire. In a seroprevalence study of 458 sexually transmitted disease (STD) clinic attendees, 142 of 145 seropositive individuals had enzyme-linked immunosorbent assay (ELISA)-positive saliva samples (97.9% sensitivity). All saliva samples from seronegative patients were ELISA-negative (100% specificity). Of the 142 ELISA-positive saliva specimens, 137 were also Western blot-positive (94.5% sensitivity). In a subsequent seroincidence study of 315 initially seronegative female prostitutes followed during 183 woman-years of observation, 9 of 14 women who seroconverted (7.7% seroincidence) had ELISA-positive saliva samples at the time seroconversion was detected. Only three of these saliva specimens could be confirmed by Western blot. Although salivary testing for HIV-1 antibodies using conventional assays was not sensitive in detecting recent seroconversions, screening of salivary samples for HIV-1 antibody provides a convenient alternative method for conducting seroprevalence surveys in populations in whom venipuncture is not possible or convenient.

Adult

Rise in prostatic cancer incidence associated with increased use of transurethral resection.

We examined the association between prostatic cancer incidence rates and the rates of transurethral prostatectomy to explore reasons for the nationally reported dramatic increases in incidence rates of prostatic cancer from 1973 through 1986. There was a strong correlation between both incidence of all stages of prostatic cancer combined and of localized disease and the increasing use of transurethral resection, a common surgical procedure usually performed to relieve urinary obstruction due to benign enlargement of the prostate. Our analyses suggest that increased detection of existing tumors via transurethral resection was the primary reason for the observed increase in incidence rates of prostatic cancer. However, analyses of mortality trends, particularly among nonwhites, and laboratory studies of the histologic nature of clinically asymptomatic tumors suggest that part of the increase may reflect changes in the real risk of prostatic cancer.

Age Factors

Comparison of the descriptive epidemiology of urinary tract cancers.

We compared the descriptive epidemiology of several urinary tract cancers, utilizing incidence data from the United States and international sources. The patterns of cancers of the renal pelvis, ureter, and urethra were more similar to those of bladder cancer than to cancer of the renal parenchyma in several ways: (i) transitional cell carcinoma is the predominant histologic type in the renal pelvis, ureter, urethra, and bladder, whereas the vast majority of renal parenchyma neoplasms are adenocarcinomas; (ii) in situ tumors often appear in all these sites except the renal parenchyma; (iii) rate ratios for renal pelvis/ureter cancers among blacks and Hispanics, relative to whites, are closer to those for bladder than to those for renal parenchymal cancers; (iv) rates among US men and women for cancers of the renal pelvis and ureter are more highly correlated with those for bladder cancer than with those of the renal parenchyma across racial groups; and (v) similar correlations occur among women across geographic areas within the US and internationally. However, the patterns for cancers of the renal pelvis and ureter do not always resemble more closely those for bladder than renal parenchyma cancers and occasionally appear different from one another. These findings indicate the importance of distinguishing tumors based on specific primary site and cell type.

Adolescent

Selenium intake, age, gender, and smoking in relation to indices of selenium status of adults residing in a seleniferous area.

Duplicate meals, serum, whole blood, and toenails were collected every 3 mo for 1 y from a group of 44 free-living adults residing in high-selenium areas of South Dakota and Wyoming to assess the relation of selenium intake to indices of selenium status. The average selenium values for the group were as follows: dietary intake, 174 +/- 91 micrograms/d (mean +/- SD), 2.33 +/- 1.08 micrograms/kg body wt; serum, 2.10 +/- 0.38 mumol/L; whole blood, 3.22 +/- 0.79 mumol/L; and toenails, 15.2 +/- 3.0 nmol/g. Selenium intake (micrograms/kg body wt) was strongly correlated (all values, P less than 0.01) with selenium concentration of serum (r = 0.63), whole blood (r = 0.62), and toenails (r = 0.59). Men and women had similar mean values of serum, whole blood, and toenail selenium despite higher selenium intakes in men. Smokers had lower tissue selenium concentrations than did nonsmokers due, at least in part, to lower selenium intake. Age was not associated with tissue selenium content. Of the variables examined selenium intake was clearly the strongest predictor of tissue selenium concentration.

Adult

Variability in nutrient and food intakes among older middle-aged men. Implications for design of epidemiologic and validation studies using food recording.

The authors conducted a dietary methodology study in 1984 in Finnish men aged 55-69 years in order to validate two dietary assessment instruments being used in the US-Finland Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Trial. Twelve 2-day food records collected from 162 men over a 6-month period, including every day of the week, served as the reference measure. This report focuses on three important questions for investigating diet and disease relations: 1) How many days are necessary to classify "usual" intake? 2) Is there loss as a result of using consecutive days? 3) Which days are necessary for assessment and classification of "usual" diet? A repeated-measures regression model was used to estimate the variance components and the effects of consecutive days, weekday (weekday vs. weekend), and season. Correlations between the averages of different numbers of days of food records and "true" usual intake were examined along with the resulting attenuations in relative risk. Results suggest that 7-14 days are required to adequately classify most individuals into categories of intake for most nutrients and some foods. There appears to be some loss of information from using consecutive days rather than days further apart. Weekday/weekend differences in mean intakes are slight, and the rank ordering of individuals appears to be preserved. A moderate seasonal effect is shown for classification of fruits, but only a slight one is seen for micronutrients and berries. Implications for the design of epidemiologic and validation studies are discussed.

Aged