Aniline, o-toluidine, 2,4-dimethylaniline, 2,6-dimethylaniline, 2,6-diethylaniline, 2,6-methylethylaniline, 2,6-diisopropylaniline, and methylene-bis-2,6-diisopropylaniline were administered to male Fischer 344 rats daily for 5, 10 or 20 days. Histopathologic evaluation of selected tissues revealed splenic congestion, increased hematopoiesis and hemosiderosis, and bone marrow hyperplasia in aniline- and o-toluidine-treated animals. These changes, characteristics consistent with enhanced erythrocytic destruction, were not observed in any of the dialkylaniline-treated animals. Hepatoxicity, characterized by biliary hyperplasia, periacinar vacuolar degeneration, hepatocytic cloudy swelling and periacinar necrosis, was observed in methylene-bis-2,6-diisopropyl-, aniline- and 2,4-dimethylaniline-treated animals. Multifocal discrete areas of necrosis were also observed in livers of animals treated with the latter compound. There were no histopathologic changes which could be attributed to any of the alkylanilines studied in kidney, esophagus, trachea, thyroid, parathyroid or urinary bladder.

Aniline Compounds↗

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High field and 2D-nmr studies with the aporphine alkaloid glaucine.

The aporphine alkaloid glaucine (1) was examined by comparison of the high field (600 MHz) 1H-nmr spectra of 1 vs. racemic 6a,7,7-trideutereoglaucine (4,5), by computer-simulated 1H-nmr spectra at 600 MHz, by using decoupled proton spectra, and two-dimensional COSY and HETCOR experiments with 1 at 500 and 360 MHz, respectively, and using high field (90 MHZ) 13C-nmr of S-(+)-glaucine (1). Emphasis was placed on the resolution of the chemical shifts and coupling constants for the H-4 alpha, H-4 beta, H-5 alpha, H-5 beta, H-6 alpha, H-7 alpha, and H-7 beta alicyclic protons of the molecule, which were previously unassigned. The complete assignment of the alicyclic protons of 1 by 1H-nmr was required for the structural elucidation of deuterated analogs of glaucine, which will be used in microbial transformation studies to determine the stereochemical course of aporphine dehydrogenation by the fungi Fusarium solani (ATCC 12823) and Aspergillus flavipes (ATCC 1030).

Aporphines↗

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Expression of matrix metalloproteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: implications for MMP inhibition therapy.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, with a very poor survival rate. Therefore there is intense scrutiny to provide a better understanding of the molecular and cellular processes involved in this aggressive disease. The matrix metalloproteinases (MMPs) are a large family of extracellular matrix degrading enzymes believed to play a crucial role in tumor invasion and metastasis. MMP inhibitors are now under development as an adjuvant approach to surgical control of NSCLC. However, there is little data available on MMPs or their tissue inhibitors (TIMPs) in NSCLC. Expression of MMP1, MMP2, MMP9, TIMP1 and TIMP2 was assessed in 44 stage II NSCLC. All proteins were found to be expressed at high levels and significant co-expression was observed. These results suggest that a broad spectrum MMP inhibitor is worthy of evaluation as a therapeutic method of reducing tumor invasion and metastasis in stage II NSCLC.

Adult↗

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Isolation and characterization of a virus associated with arthritis of chickens.

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Animals↗

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Carbohydrate metabolism in chicks after administration of toxins from a Phomopsis sp.

Soybeans inoculated with Phomopis sp. were incubated for weeks and then extracted with methanol and ether, and the culture filtrates were intubated into crops of chicks. Activities of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase in liver were increased, and glycogen stores and plasma glucose concentrations were reduced. Histologically, severe hepatocytic necrosis was found in chicks treated with the toxic culture filtrate. Significant clinical signs were loss of body weight and reduced feed consumption. The metabolic changes responsible for the findings are discussed.

Animals↗

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Severity of tenosynovitis in reovirus-infected chickens fed various dietary levels of choline, folic acid, manganese, biotin, or niacin.

Five experiments were conducted to determine the incidence and severity of tenosynovitis in tendons distal to the tarsal joint in 4-, 6-, and 8-week-old reovirus WVU 2937-infected chickens fed diets containing 20%, 100%, or 200% of the 1977 National Research Council nutrient requirements (NCR-77) of manganese, biotin, niacin, choline, or folic acid. Male chickens, but not female chickens, fed 20% or 100% or the NRC-77 level of folic acid had consistently higher lesion scores of tenosynovitis than male chickens fed the 200% NRC-77 level of folic acid. Increasing dietary manganese levels from 20% to 200% NRC-77 reduced the severity of tendon swelling in 6- and 8-week-old male chickens and appeared to increase the severity of tendon swelling in 8-week-old female chickens. Male chickens fed 20% of the NRC-77 required level of biotin had numerically more severe tenosynovitis at 6 weeks of age and significantly more severe tenosynovitis at 8 weeks of age than male chickens fed 100% and 200% of the NRC-77 level of biotin. Increasing dietary choline levels from 20% to 200% of the NCR-77 required level increased the severity of tenosynovitis numerically at 6 weeks of age and significantly at 8 weeks of age. When data were pooled across diet, male chickens had significantly more severe tenosynovitis than female chickens at 4, 6, and 8 weeks of age in the choline experiment and at 4 and 6 weeks of age in the folic acid experiment. Differences in the severity of tenosynovitis of individual treatment means (sex X diet X infection interaction means) occurred at only the 20% or 100% NRC-77 level of choline or folic acid. Male chickens also had more severe tenosynovitis than female chickens when fed 20% of the NRC-77 required level of manganese for 6 or 8 weeks.

Age Factors↗

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Responses of specific-pathogen-free chicks to concomitant infections of reovirus (WVU-2937) and infectious bursal disease virus.

Specific-pathogen-free white leghorn chicks concomitantly infected with both infectious bursal disease virus (IBDV) and reovirus (WVU-2937) on day 1 had significantly lower (P less than 0.05) virus-neutralizing- and precipitating-antibody geometric mean titers (GMT) to reovirus than chicks infected with only reovirus on day 1 but had a similar incidence of inflammation of the metatarsal digital flexor tendons. Chicks infected with IBDV on day 7 and reovirus on day 14 had a greater incidence of inflammation of the tarsometatarsal digital flexor tendons and lower neutralizing- and precipitating-antibody GMT to reovirus than chicks infected with only reovirus on day 14. Chicks infected with both viruses on day 1 had a significantly lower (P less than 0.05) neutralizing-antibody GMT to IBDV than chicks infected with only IBDV.

Animals↗

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Further observations on enterovirus infection in specific-pathogen-free turkey poults.

To evaluate sites of enterovirus replication and to characterize the resulting lesions, twenty 4-day-old specific-pathogen-free (SPF) turkey poults were orally inoculated with an enterovirus. Twenty uninoculated SPF poults served as controls. Inoculated poults were depressed, had ruffled feathers, watery droppings, and pasted vents. Gross lesions were dilated thin-walled ceca with foamy yellow fluid. Immune electron microscopy of the gastrointestinal tract contents revealed an enterovirus with an average diameter of 23.5 nm. Immunoperoxidase and indirect immunofluorescent antibody assays revealed intracytoplasmic staining in enterocytes of the duodenum, jejunum, and ileum. This correlated with the scanning electron microscopy findings, which showed the most lesions in the jejunum and ileum. The ileum had prominent cell outlines because of rounded, distinct, bulging epithelial cells. Histopathology revealed slight shortening of villi and increased crypt depth in the intestines of inoculated poults. Our findings indicate that the small intestine is the site of turkey enterovirus replication, and the gross and microscopic changes observed are determined to result from viral damage to the enterocytes.

Animals↗

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Mycotoxicosis in chicks produced by toxins from Phomopsis sp. or Diaporthe phaseolorum var. sojae.

The possibility of producing toxic effects in day-old chicks with mycotoxins from Phomopsis sp. or Diaporthe phaseolorum var. sojae isolates was studied. Evidence was found that Phomopsis sp., but not Diaporthe, produces hepatic necrosis with high mortality in chicks. Enzymatically, the hepatotoxin produced by Phomopsis sp. caused an increase in the level of liver glucose-6-P dehydrogenase. Mycotoxicosis caused by Phomopsis sp. was compared with lupinosis.

Animals↗