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Biomedical subjects

C C Brown

Publications and source records attributed to C C Brown.

At least 55 records · Page 3Linked to original sources
PubMed1996

Immunohistochemical detection of rinderpest virus: effects of autolysis and period of fixation.

Samples of eyelid, tongue, soft palate and palatine tonsil were collected from calves infected experimentally with rinderpest virus. The tissues were fixed in 10 per cent neutral buffered formalin immediately, 24 or 48 hours post mortem. Then, after three days, 10 days, 28 days or three months in formalin, they were processed into paraffin blocks and examined immunohistochemically for rinderpest viral antigen. The tonsil was the best of the four tissues in providing a consistently positive immunohistochemical signal for the presence of virus, despite autolytic changes and/or prolonged fixation.

Animals↗
PubMed1996

Pathogenesis of wild-type and leaderless foot-and-mouth disease virus in cattle.

Four calves were experimentally infected via aerosol with foot-and-mouth disease virus. Two were infected with a wild-type virus derived from a full-length infectious clone (A12-IC), and two were infected with a clone-derived virus lacking the leader gene (A12-LLV2), with euthanasia and tissue collection at 24 and 72 h postexposure (hpe). Clinical disease was apparent only in the animal given A12-IC and euthanized at 72 hpe. In situ hybridization revealed that the animal infected with A12-IC and euthanized at 24 hpe had abundant viral nucleic acid in the lung, present in clusters of positive cells in the respiratory bronchiolar epithelium and associated subepithelial regions. At 72 hpe in the A12-IC-infected calf, viral nucleic acid in the lung was present in interstitial areas, and in addition, viral nucleic acid was detectable in epithelial tissues around histologically apparent vesicles. In animals infected with A12-LLV2, viral nucleic acid was detectable in the lung at both 24 and 72 hpe, but staining revealed a more localized distribution with less nucleic acid than was found in animals given A12-IC. Therefore, it appears that after aerosol exposure to A12-IC, early replication is in the region of the lung, with subsequent dissemination to distal sites. In comparison, the A12-LLV2 virus is much less widely disseminated in the lung at 24 hpe, with no lesions or virus detectable in secondary sites at 72 hpe. The greatly reduced pathogenicity of A12-LLV2 may make it an excellent candidate for a modified live viral vaccine.

Animals↗
PubMed1996

Distribution of bluetongue virus in tissues of experimentally infected pregnant dogs as determined by in situ hybridization.

Six female dogs (four pregnant and two nonpregnant) were inoculated with bluetongue virus (BTV), serotype 11. Pregnant animals and one nonpregnant dog received 5.5-6.3 log10 of cell culture-adapted virus. The other nonpregnant dog received a modified live vaccine contaminated with bluetongue virus. The non-pregnant animals never became clinically ill and were euthanatized 35 days post-inoculation. Three of the four pregnant dogs aborted, and all four died or were euthanatized 5-10 days post-inoculation. The predominant pathologic feature in the adults was severe pulmonary edema. Various tissues from the bitches and fetuses were examined by in situ hybridization using a digoxigenin-labeled probe corresponding to the nonstructural protein-1 gene of BTV-17. By this technique, viral nucleic acid was detected predominantly in endothelial cells of lung of all four dogs, with lesser amounts in capillaries of uterus, spleen, and kidney in some of the dogs. In two adult dogs, bluetongue viral nucleic acid was detected in mononuclear cells of the periarteriolar lymphoid sheaths of spleen. There was minimal staining of capillaries in placenta in three of the five fetuses examined. There was no viral nucleic acid detected in any of the other fetal tissues.

Animals↗
PubMed1996

Estimates of human fertility and pregnancy loss.

OBJECTIVE: To examine the fertility and pregnancy wastage rates in a group of presumably fertile couples. DESIGN: Prospective observational study of 200 couples desiring to achieve pregnancy over 12 menstrual cycles coupled with pregnancy outcome follow-up. SETTING: A university-based obstetrics and gynecological center. PATIENTS: Personal interviews and questionnaires were used to screen couples for entry into the study. Couples were counseled to have intercourse centered on predicted day of ovulation. Phase 1 included the first three cycles in which women collected daily morning urine samples, underwent midcycle postcoital tests, and, if late for their menses, presented for serum hCG testing. Phase 2 encompassed the next nine cycles in which women were contacted monthly by phone and underwent serum hCG testing if menses was delayed. Urine samples from cycles in which clinical (serum hCG) pregnancy did not occur underwent sensitive hCG testing to detect occult pregnancies. Pregnancies were followed until delivery to ascertain outcome. RESULTS: Eighty-two percent of the 200 couples followed for the entire study period conceived. The maximal fertility rate was approximately 30% per cycle in the first two cycles. This rate quickly tapered over the remainder of the study. Pregnancy wastage during phase 1 accounted for 31% of the pregnancies detected. Forty-one percent (15/36) of these losses were seen only by urine hCG testing and were categorized as occult. Eleven of these same patients later achieved clinically recognized conceptions during the study. CONCLUSIONS: These results support the concept that the efficiency of human reproduction is maximum at approximately 30% per cycle. A very significant number of these pregnancies end in spontaneous abortion. In addition, pregnancy loss before missed menses occurs in a significant proportion of women.

Abortion, Spontaneous↗
PubMed1996

Colorectal cancer and folate status: a nested case-control study among male smokers.

Evidence is accumulating that folate, a B vitamin found in green leafy vegetables, may affect the development of neoplasia. We examined the relationship between folate status and colorectal cancer in a case-control study nested within the Alpha-Tocopherol Beta-Carotene Study cohort of male smokers 50-69 years old. Serum folate was measured in 144 incident cases (91 colon, 53 rectum) and 276 controls matched to cases on baseline age, clinic, and time of blood collection. Baseline dietary folate was available from a food-use questionnaire for 386 of these men (92%). Conditional logistic regression modeling was used. No statistically significant association was observed between serum folate and colon or rectal cancer. Although a 2-fold increase in rectal cancer risk was suggested for men with serum folate > 2.9 ng/ml and those in the highest quartile of energy-adjusted folate intake, there was no evidence of a monotonic dose-response, and all confidence intervals included unity. For dietary folate and colon cancer, odds ratios of 0.40 [95% confidence interval (CI), 0.16-0.96], 0.34 (95% CI, 0.13-0.88), and 0.51 (95% CI, 0.20-1.31) were obtained for the second through fourth quartiles of energy-adjusted folate intake, respectively, compared to the first (P for trend = 0.15). Furthermore, men with a high-alcohol, low-folate, low-protein diet were at higher risk for colon cancer than men who consumed a low-alcohol, high-folate, high-protein diet (OR, 4.79; 95% CI, 1.36-16.93). This study suggests a possible association between low folate intake and increased risk of colon cancer (but not rectal cancer) and highlights the need for further studies that measure dietary folate and methionine, along with biochemical measures of folate (i.e., erythrocyte and serum), homocysteine, and vitamin B12.

Aged↗
PubMed1995

Chemopreventive activity of tamoxifen, N-(4-hydroxyphenyl)retinamide, and the vitamin D analogue Ro24-5531 for androgen-promoted carcinomas of the rat seminal vesicle and prostate.

We evaluated the ability of dietary N-(4-hydroxyphenyl)retinamide; 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (Ro24-5531); and tamoxifen to inhibit the development of androgen-promoted carcinomas of the accessory sex organs of male Lobund-Wistar rats. Invasive carcinomas of the seminal vesicle (SV) and anterior prostate (AP) were induced in Lobund-Wistar rats with three different combinations of initiator [N-nitroso-N-methylurea (NMU)] and promoter [testosterone propionate (TP)]: (a) high-dose NMU (30 mg/kg) + high-dose TP (20 mg via implant every 2 months); (b) high-dose NMU + low-dose TP (10 mg implanted every 2 months); or (c) low-dose NMU (15 mg/kg) + low-dose TP. During the period of TP administration, rats were fed a diet supplemented with either N-(4-hydroxyphenyl)retinamide (1 or 2 mmol/kg diet), Ro24-5531 (1.25 or 2.5 nmol/kg diet), tamoxifen (0.5 or 5 mg/kg diet), or vehicle alone. After sacrifice at 8.5 or 11 months, the prostate-seminal vesicle complex from each rat was processed in toto and histologically staged as to the extent of tumor involvement. In animals given low-dose TP, all three agents were significantly effective at reducing the incidence of invasive carcinomas of the SV and, to a lesser degree, the AP. Of the three agents, tamoxifen given in high dose (5 mg/kg) had the strongest activity, reducing the occurrence of invasive SV carcinomas from 72-83% in controls to 6% (P = 0.0001) and the occurrence of invasive AP carcinomas from 50-72% to 18-22% (P < 0.05).

Androgens↗
PubMed1995

Seizure-induced lumbar burst fracture.

STUDY DESIGN: This case report illustrates how muscle forces generated during generalized seizure activity can result in severe musculoskeletal trauma. A case is presented of a 35-year-old man who suffered seizure-induced contiguous L1 and L2 lumbar burst fractures. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, there have been no reports of seizure-associated lumbar burst fractures. OBJECTIVE: The case is presented to demonstrate how seizure activity can lead to lumbar burst fractures. METHODS: A 35-year-old man suffered a witnessed tonic-clonic seizure while lying on a couch. He had no other trauma and no history of previous seizure activity. As his mental status cleared in the post-ictal period, he complained of mild low back pain. Upon ambulation, he continued to complain of persistent low back pain. Plain radiographs obtained on hospital visit day 5 identified the L1 and L2 contiguous burst fractures. Initial treatment using a Risser cast was unsuccessful, and the patient subsequently underwent posterior spine fusion with Cotrel-Dubousset segmental instrumentation and an iliac crest bone graft. RESULTS: At 1-year follow-up, the patient's spine was stable with no evidence of pseudoarthrosis or further kyphosis. He was maintained on anti-seizure medication. CONCLUSIONS: Forces generated during a tonic-clonic seizure can result in axial skeletal trauma, including thoracic and lumbar burst fractures. Clinical signs of unstable fractures may be subtle. A high index of clinical suspicion is warranted for patients who experience tonic-clonic seizures and who have associated risk factors.

Adult↗
PubMed1995

Optimization of an in situ hybridization technique for the detection of foot-and-mouth disease virus in bovine tissues using the digoxigenin system.

An in situ hybridization technique has been optimised for use on paraffin-embedded sections of tissues collected from cattle infected experimentally with foot-and-mouth disease virus type O1BFS. Tissue was collected 5 days after infection by direct contact. In situ hybridization was carried out using an RNA probe corresponding to a region of the 3D gene which codes for the RNA polymerase, and labelled with digoxigenin. Consistent, reproducible signal was detected within the epithelial layers of the palatine tonsil, soft palate and pharyngeal tissue studied. This is the first time that a digoxigenin-based system has been used successfully for FMD virus RNA detection with bovine tissue samples.

Animals↗
PubMed1995

Pathogenesis of foot-and-mouth disease in swine, studied by in-situ hybridization.

Eight 7-month-old pigs were inoculated intradermally with 10(3) plaque-forming units of foot-and-mouth disease virus, type O, and killed 24, 48, 72, or 96 h later. Numerous tissues from each animal were collected and examined histopathologically and by in-situ hybridization to determine the presence of virus and its correlation with lesion development. The probe for in-situ hybridization was a biotinylated 500-base negative-sense transcription product corresponding to a portion of the gene encoding polymerase. With this technique, virus was shown to be widely disseminated in all epidermal tissues, regardless of histologically apparent cellular disruption.

Animals↗
PubMed1995

Possible immunologic involvement of antioxidants in cancer prevention.

The people of Linxian County, China have one of the world's highest rates of esophageal cancer. Two intervention trials were conducted to determine whether supplementation with specific vitamins and minerals could lower mortality from or incidence of cancer in this population and whether supplementation with multiple vitamins and minerals would reduce esophageal and gastric cardia cancer in persons with esophageal dysplasia. About 30,000 general population (GP) subjects in the GP trial were randomly assigned to one of eight intervention groups according to a one-half replicate of a 2(4) factorial experimental design and were supplemented for 5.25 y with four combinations of micronutrients at doses from one to two times the US recommended dietary allowance (RDA). About 3000 subjects in whom dysplasia was diagnosed in the dysplasia trial were randomly assigned to groups receiving daily supplementation with 14 vitamins and 12 minerals at two to three times the US RDA or placebo for 6 y. Results of the dysplasia trial indicate that in individuals with esophageal dysplasia, micronutrient supplementation had little effect on T lymphocyte responses. In contrast, male participants in the GP trial who were supplemented with beta-carotene, vitamin E, and selenium showed significantly (P < 0.05) higher mitogenic responsiveness of T lymphocytes in vitro than those not receiving these micronutrients.

Adult↗
PubMed1995

Effects of alcohol consumption on lipoproteins of premenopausal women. A controlled diet study.

A substantial portion of American women consume alcohol, but controlled studies of alcohol-induced changes in lipoproteins of women are rare. In this study, the effects of alcohol consumption (equivalent to two drinks per day) on the lipoprotein profiles of 34 premenopausal women were measured while controlling subjects' diet and various other potentially confounding variables including phase of the menstrual cycle. Alcohol and no-alcohol treatments were administered in a crossover design, and blood samples were obtained during the early follicular phase of the third month of treatment. With alcohol, HDL cholesterol levels increased 10%, LDL levels decreased 8%, and levels of lipoprotein(a) were unchanged. The increase in HDL cholesterol was due to an increase in both HDL2 and HDL3, and the overall size of HDL particles was increased. HDL particles containing apolipoprotein (apo) A-I and apoA-II as well as those containing apoA-I but no apoA-II were elevated in response to alcohol. Although these observations are limited to a single phase of the menstrual cycle, the alcohol-induced changes in lipoproteins are consistent with changes that are thought to confer protection against coronary heart disease.

Adult↗
PubMed1994

Can energy adjustment separate the effects of energy from those of specific macronutrients?

Energy adjustment is used in nutritional epidemiology in an attempt to separate specific effects of macronutrients (carbohydrate, fat, and protein) from one another and from the generic effect of the total quantity of energy consumed. However, models in which the risk of disease is allowed to depend simultaneously on daily total energy consumption and separate components of energy that sum to the total are not identifiable: the specific effects of individual macronutrients and the generic effect of energy cannot be disentangled by multivariate analysis. The standard, residual, and partition methods exclude one or more macronutrients from consideration, thereby allowing estimation, but the parameters that are estimated no longer represent specific macronutrient or generic energy effects. Therefore, an interpretation of a regression coefficient from these methods as a specific effect of a macronutrient or as the generic effect of energy requires additional, almost always questionable, assumptions. For example, a conclusion based on data alone that there is a specific fat effect upon the development of breast cancer but no specific effects of other macronutrients and no generic energy effect is not possible. Notwithstanding these serious problems, some useful etiologic inference still can be made.

Energy Metabolism↗
PubMed1994

Prevention of breast cancer in the rat with 9-cis-retinoic acid as a single agent and in combination with tamoxifen.

We show that 9-cis-retinoic acid (9cRA) is a potent inhibitor of mammary carcinogenesis induced by N-nitroso-N-methylurea in Sprague-Dawley rats. Rats were first treated with a single dose of N-nitroso-N-methylurea (50 mg/kg body weight) and then fed non-toxic levels of 9cRA (120 or 60 mg/kg of diet). 9cRA was highly effective in reducing tumor incidence, average number of tumors per rat, and average tumor burden, as well as extending tumor latency. The combination of 9cRA with low levels of tamoxifen (TAM; fed at either 1.0 or 0.5 mg/kg of diet) was particularly effective; addition of 9cRA to a TAM regimen doubled the number of animals that were tumor-free at autopsy and significantly diminished tumor number and tumor burden. For suppression of carcinogenesis in vivo, 9cRA was much more potent than all-trans-retinoic acid, both as a single agent or in combination with TAM, although both retinoids had equivalent inhibitory effects on DNA synthesis in cultured human breast cancer cell lines. Both 9cRA and all-trans-retinoic acid induce the expression of the adhesion molecule, E-cadherin, in the SK-BR-3 cell line. We suggest that clinical evaluation of the combination of 9cRA and TAM, either for chemoprevention or for adjuvant therapy, should be considered.

Animals↗
PubMed1994

Energy adjustment methods for nutritional epidemiology: the effect of categorization.

The authors discuss the interpretation of four alternative energy adjustment methods (Residual, Standard, Partition, and Nutrient Density) that have been proposed for the analysis of nutritional epidemiology studies. These methods have so far been compared under circumstances where intake of the nutrient of interest is measured as a continuous variable. Because it is common practice to categorize nutrient intakes in the analysis, the authors investigate the effect of such categorization on the interpretation of results from the four methods with the use of computer simulations and statistical theory. They consider four cases: where the nutrient intake is either divided into quartiles or ordered so as to investigate trend over the quartile groups, combined with using an adjusting variable that is either continuous or categorized. The results show: 1) the Residual, Standard, and Partition methods are no longer equivalent as they are in the continuous case; 2) compared with the Standard method, the Residual method appears to be more powerful for detecting trends in relative odds, is more robust to residual confounding when the adjustment variable is categorized, and provides more meaningful odds ratios; and 3) the Residual and Nutrient Density methods give closely similar results.

Bias↗
PubMed1994

Seizure-induced thoracic burst fractures. A case report.

Musculoskeletal injuries can arise from muscle contraction during generalized seizure activity. The most frequently documented injuries are thoracic vertebral body compression fractures, proximal femur fractures, and proximal humerus fractures occasionally accompanied by dislocation. A case is presented of a thoracic burst fracture and bilateral proximal humerus fractures secondary to a seizure.

Adult↗
PubMed1994

Elevated levels of tumor necrosis factor-alpha in Zairian neonate plasmas: implications for perinatal infection with the human immunodeficiency virus.

Plasma levels of tumor necrosis factor-alpha (TNF alpha) and the ability of plasmas to induce HIV expression in chronically infected cell lines were measured in samples from adults, cord blood, and neonates from Zaire and North America. Plasma levels of TNF alpha were higher in Zairian neonates born to HIV-negative and -positive mothers than in uninfected Zairian adults (612 vs. 128 vs. 8 pg/mL, P < .001); this dichotomy persisted until children were 9 months old. Plasmas from neonates of HIV-negative Zairian mothers also stimulated higher levels of reverse transcriptase from HIV-infected cell lines than did plasma from HIV-negative Zairian adults (1339 vs. 110 cpm, P < .001). Similar patterns were noted in plasmas from HIV-negative North American adults and neonates; however, TNF alpha levels were markedly lower, and smaller differences were noted among North American adults and neonates than those in the Zairian cohort. Markedly elevated plasma TNF alpha levels in Zairian neonates and infants may play a role in the pathogenesis and progression of HIV disease in this patient population.

Adult↗
PubMed1994

Distribution of antigen in cattle infected with rinderpest virus.

Five Holstein heifers (approximately 8 months of age and weighing 225-275 kg) were inoculated subcutaneously with 1,000 TCID50 of rinderpest virus, virulent Kabete O strain. They become clinically ill 2 to 5 days post-inoculation, with fever (40 C to 41.5 C), conjunctivitis, and diarrhea. All were euthanatized when moribund at 6 days postinoculation. The following tissues were collected in formalin, embedded in paraffin, and subsequently subjected to histopathologic and immunohistochemical examination: tongue, buccal mucosa, soft palate, esophagus, rumen, abomasum, duodenum, jejunum with and without Peyer's patch, ileum, cecum, proximal colonic lymphoid patch, spiral colon, eyelid, gall bladder, spleen, tonsil, trachea, lungs, and numerous lymph nodes. Immunohistochemical examination was accomplished using a primary rabbit anti-rinderpest antibody, and either a peroxidase-diaminobenzidine or alkaline phosphatase-Vector Red detection substrate system. In the lymph nodes, spleen, and tonsil, depletion of lymphocytes from all areas was extensive, with antigen most prominent in persisting reticular cells throughout the tissues. In the intestine, necrotizing and ulcerative changes in the mucosa were extensive and widespread. Damage was most severe in areas overlying lymphoid patches. In both small and large intestine, antigen was distributed predominantly in epithelial cells, histiocytic cells in the lamina propria, and in remaining reticular cells of lymphoid patches. In oral mucosa, there were multiple ulcerations and numerous multinucleate syncytial cells, both containing and without antigen. Lungs and trachea had subtle yet consistent necrosis of epithelial cells, with antigen often distributed in a circumferential manner in epithelium of bronchioles.

Animals↗