Verrucosamide,a Cytotoxic 1,4-Thiazepane-Containing Thiodepsipeptide from a Marine-Derived Actinomycete

A new cytotoxic thiodepsipeptide, verrucosamide (1), was isolated along with the known, related cyclic peptide thiocoraline, from the extract of a marine-derived actinomycete, a Verrucosispora sp., our strain CNX-026. The new peptide, which is composed of two rare seven-membered 1,4-thiazepane rings, was elucidated by a combination of spectral methods and the absolute configuration was determined by a single X-ray diffraction study. Verrucosamide (1) showed moderate cytotoxicity and selectivity in the NCI 60 cell line bioassay. The most susceptible cell lines were MDA-MB-468 breast carcinoma with an LD₅₀ of 1.26 µM, and COLO 205 colon adenocarcinoma with an LD₅₀ of 1.4 µM. Also isolated along with verrucosamide were three small 3-hydroxy(alkoxy)-quinaldic acid derivatives that appear to be products of the same biosynthetic pathway.     

Long-term study of aerobic bacteria of the genital tract in stud dogs.

The aerobic bacterial flora of the genital tract was characterized in 15 stud dogs in an 18-month study. The dogs represented 4 breeds and were from 3 kennels. Bacterial samples from the prepuce and semen were collected every month, except in connection with matings, when they were collected weekly (464 samples). The dogs that were included all mated at least once during the study. The mean pregnancy rate, litter size, and pup mortality for the bitches with which they had mated were all within normal limits. The most frequent bacteria isolated from the prepuce and semen were Pasteurella multocida, beta-hemolytic streptococci, and Escherichia coli. There was a tendency for breeds to differ in frequency of the most common bacterial species. Bacterial culture yielded no aerobic growth in 14.2% of the preputial samples and 69.8% of the semen samples. Bacteria were transferred between dog and bitch at mating. In this study of healthy breeding dogs, neither the fertility of the dog nor that of the bitch was affected by the bacteria transferred.     

Clinical response of nasal adenocarcinoma to cisplatin chemotherapy in 11 dogs.

In 11 dogs with nasal adenocarcinoma, IV treatment with 2 to 8 cycles of cisplatin at a dosage of 60 mg/m2 of body surface, given at 3-week intervals, resulted in a survival time of 8 to 128 weeks (mean, 32.7 weeks; median, 20 weeks). Radiography revealed complete remission in 2 dogs and partial remission in 1 dog, for an overall response rate of 27%. Clinical problems such as nasal discharge (n = 11), sneezing (n = 6), and epistaxis (n = 4) resolved in 1 to 2 weeks in all dogs after beginning chemotherapy.     

Immunodeficiency associated with lymphosarcoma in a horse.

Immune system dysfunction and immunoglobulin deficiency was diagnosed in a 2-year-old horse with disseminated lymphosarcoma. Prolonged (35 days) parenteral nutrition was delivered to support the horse during a period in which immune function studies could be performed. Correction of nutritional compromise by use of parenteral nutrition did not correct the immunoglobulin deficiency, and results of lymphocyte phenotype testing did not indicate abnormal proportions of leukocytes. Lymphoblast transformation studies were suggestive of a circulating immunosuppressive factor in the horse's serum. Normal cell function was detected when the cells were stimulated in precolostral equine serum.     

Cryptococcal osteomyelitis in a dog

Osteomyelitis caused by Cryptococcus neoformans was diagnosed in a three-year-old male Irish wolfhound. The case details and radiological findings of radiolucency and periosteal reaction of the left third metatarsal bone had lead to an initial diagnosis of a malignant bone tumour. Biopsy revealed a fungal granuloma and culture identified the causal organism. A four month course of ketaconazole was instigated and the lameness resolved. Twelve months after the end of treatment there was no recurrence of the problem.     

Factors affecting skim milk progesterone assay results.

Five studies were performed to determine factors affecting progesterone concentration in skim milk. Results of the first study indicated that progesterone concentration was higher in skim milk of samples kept 16 hours in an ice bath (0 C) than of those left at room temperature (21 C). In the second study, this temperature effect was found to be reversible, with skim milk progesterone concentration increasing when whole milk samples were cooled prior to centrifugation. In the third study, [3H]-labeled progesterone was used to determine the relationship between fat content of foremilk (the first milk obtained from the teats), midmilk (milk obtained midway through milking), and strippings (milk obtained immediately after milking machines have been removed) samples and temperature (4 C and 21 C) on the percentage of progesterone in the skim milk fraction. The relationship between percentage of butterfat and percentage of progesterone in skim milk was linear when the log of these variables was used for calculations. In the fourth study, assayable progesterone in the skim milk fraction of foremilk, midmilk, and strippings was affected by temperature. In the fifth study, a multiple-regression procedure was used to determine the amount of variation in percentage of radioactive progesterone in the skim milk fraction. Independent variables (whole milk butterfat and temperature of incubation [1, 3, 13, 22, 37, and 50 C]) and the natural log of each variable, were entered into a stepwise multiple-regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bovine spongiform encephalopathy: epidemiological features 1985 to 1990.

Following the identification of bovine spongiform encephalopathy (BSE) in the British cattle population in 1986 epidemiological studies were launched. This paper provides an updated account of the epidemiological features of BSE from 1985, when the first cases, based on clinical histories, occurred, until 1990. The number of cases up to December 1989 represents an annual incidence of 3.9 confirmed cases per 1000 adult animals in Great Britain. Many more dairy herds were affected than beef suckler herds, a difference attributable to the difference in feeding practices between the two herd types. The geographical variation in incidence previously described has persisted with the highest incidence in the south and east of England. Other features of the epidemiology, including the low within-herd incidence, remained unaltered from the earlier findings. The results support the previously suggested hypothesis that the outbreak of BSE was due to the sudden exposure of the cattle population to a scrapie-like agent in 1981/82. There was no evidence of direct transmission between cattle during the period considered.