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Swine leukocyte antigen (SLA) diversity in Sinclair and Hanford swine.

The swine leukocyte antigen (SLA) haplotype B is associated with increased penetrance of the tumor traits in Sinclair swine cutaneous melanoma (SSCM). We established a series of SinclairxHanford swine crosses to facilitate genetic mapping of the tumor-associated loci. In this study, the SLA diversity in the founding animals was characterized for effective selection of maximum tumor penetrance in the pedigrees.

Role of selection and inbreeding on the incidence of cutaneous malignant melanoma in Sinclair swine.

This paper reports the quantitative analysis of the historical database of a herd of Sinclair swine affected by cutaneous malignant melanoma. The herd was under partial and non-systematic selection for melanoma susceptibility (animals having at least one tumour during the first 6 weeks of life). Weighted selection differentials for the number of tumours at birth and the number of tumours at 6 weeks were generally positive and between -0.

Spontaneous regression of cutaneous melanoma in sinclair swine is associated with defective telomerase activity and extensive telomere erosion.

Recently we proposed the hypothesis that extensive telomeric association of chromosomes is an early manifestation of cell death and asked whether there are extensive telomeric associations present in metaphases of the spontaneously regressing Sinclair swine cutaneous melanoma (SSCM). Our results indicate that early passage SSCMs, in the accelerated growth phase, do not show telomeric associations but do have numerical and other specific structural abnormalities. However, the same melanoma cell lines at late passages or melanomas obtained from middle- and old-aged Sinclair swine show extensive telomeric associations in the form of dicentric, multicentric, and ring configurations.

Basal and stress-induced corticosterone levels in olive ridley sea turtles (Lepidochelys olivacea) in relation to their mass nesting behavior.

Adrenocortical responsiveness to turning stress was examined in wild, reproductively-active olive ridley sea turtles (Lepidochelys olivacea) in relation to their mass nesting (arribada) behavior. We hypothesized that the high sensitivity threshold (HST) observed in ovipositing sea turtles is associated with a diminished sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to stressful stimuli in arribada females. We tested this hypothesis by determining whether arribada females exhibited an increased activation threshold of the HPA axis to an imposed stressor (turning stress).

Lipid A mutant Salmonella with suppressed virulence and TNFalpha induction retain tumor-targeting in vivo.

Systemically administered tumor-targeted Salmonella has been developed as an anticancer agent, although its use could be limited by the potential induction of tumor necrosis factor alpha (TNFalpha)-mediated septic shock stimulated by lipid A. Genetic modifications of tumor-targeting Salmonella that alter lipid A and increase safety must, however, retain the useful properties of this bacteria. We report here that disruption of the Salmonella msbB gene reduces TNFalpha induction and increases the LD50 of this pathogenic bacteria by 10,000-fold.

Seasonal reproductive cycle of the Kemp's ridley sea turtle (Lepidochelys kempi).

The seasonal reproductive cycle of the Kemp's ridley sea turtle (Lepidochelys kempi) was studied under seminatural conditions at the Cayman Turtle Farm, Grand Cayman, British West Indies, from June 1987 to July 1988. Male L. kempi displayed a prenuptial rise in serum testosterone 4 to 5 months prior to the mating period (March).

Regression by differentiation in the Sinclair swine model of cutaneous melanoma.

The spontaneous regression of melanoma in Sinclair miniature swine involves the replacement of tumours by pigmented cells, hitherto interpreted as pigment-laden macrophages (PLMs). We hypothesized that these residual cells are terminally differentiated melanoma cells, not monocyte-derived macrophages. Swine melanoma explants with no regression were transplanted into severe combined immunodeficient (SCID) mice.

Genetic predisposition and specific chromosomal defects associated with Sinclair swine malignant melanomas.

Cytogenetic abnormalities are the hallmarks of most cancers and cutaneous melanomas are no exception. The purpose of this study was to determine whether nonrandom chromosomal abnormalities are associated with development and spontaneous regression of congenital cutaneous melanoma in Sinclair miniature swine. Careful analyses of the peripheral blood lymphocytes, skin fibroblasts, and melanoma cell lines of Sinclair swine indicated telomeric association, genetic instability, and clonal marker formations involving swine chromosomes 2, 3, 6, 7, 12, and 17.

Immunophenotypic characterization of tumor infiltrating lymphocytes and peripheral blood lymphocytes isolated from melanomatous and non-melanomatous Sinclair miniature swine.

Selectively-bred Sinclair miniature swine exhibit a high incidence of congenital malignant melanoma which either proves fatal (10-15% of tumor-bearing piglets) or spontaneously regresses with a biphasic immunological phenomenon (85-90%) and no recurrence of malignancy. Mononuclear leukocytes were isolated from cutaneous melanomas and peripheral blood specimens collected from melanomatous (tumor-bearing) Sinclair swine during second-phase regression, and from peripheral blood specimens collected from non-melanomatous (tumor-free) Sinclair swine and control Hanford swine. Leukocyte identities were determined with single- and dual-parameter indirect immunofluorescence assays via flow cytometry.

Cycloheximide-induced apoptosis in melanoma cells derived from regressing cutaneous tumours of Sinclair swine.

The role of apoptosis in the spontaneous regression of Sinclair swine melanoma was investigated in vitro with swine melanoma cell lines. Growth characteristics and sensitivity to cycloheximide-induced apoptosis were determined in melanoma cell lines derived from tumours that were progressing or undergoing regression in vivo. In contrast to cell lines derived from progressing tumours, those derived from regressing tumours showed induction of apoptosis; this phenomenon was dependent on dose but independent of cell growth stage in culture.

Genetic determinants of cutaneous malignant melanoma in Sinclair swine.

The role of genetic factors involved in the determination of risk of cutaneous malignant melanoma (CMM) in humans remains unclear owing to genetic heterogeneity and reliance on simplistic models of inheritance. Here, we report a statistical genetic analysis of cutaneous malignant melanoma in Sinclair swine (SSCM), a unique animal model for human CMM. Using complex segregation analysis a two-locus model involving an unknown major locus and a second locus that lies within or close to the swine leukocyte antigen (SLA) complex jointly determine risk of SSCM in pedigreed animals.

Histopathology of regression in sinclair swine model of melanoma.

Background: Detailed histopathologic studies of melanomas occurring in neonatal Sinclair miniature swine have demonstrated a remarkable similarity to human melanoma. A significant difference is the predictable, complete regression of primary and metastatic tumors that occurs in all animals by early adulthood (1 to 2 years). Prior histopathologic descriptions of regression in this model have been incomplete with regard to the time of onset and chronologic sequence of events.

Common swine leucocyte antigen (SLA) haplotypes in NIH and Sinclair miniature swine have similar effects on the expression of an inherited melanoma.

Mixed lymphocyte culture and serological typing of NIH and Sinclair miniature swine indicate that the two herds share a common SLA haplotype. NIH haplotype a (International Haplotype H10) appears identical to Sinclair haplotype B, which has significant effects on the penetrance of Sinclair swine cutaneous malignant melanoma (SSCM). Offspring of crosses between melanoma-bearing Sinclair swine homozygous for the B haplotype and non-melanoma NIH aa swine have tumour incidence identical to Sinclair melanoma BB x Sinclair non-melanoma BB offspring.

Establishment and characterization of four Sinclair swine cutaneous malignant melanoma cell lines.

Cutaneous malignant melanoma of Sinclair Swine (SSCM) is a heritable, congenital neoplasm which either proves fatal to the neonatal animal or undergoes spontaneous regression. Four SSCM cell lines, UISO-SSCM-433, UISO-SSCM-438, UISO-SSCM-5052, and UISO-SSCM-8093, were derived from biopsy specimens of primary tumors removed from swine at 26, 8, and 8 weeks of age, and 15 weeks gestation, respectively. Morphologic features, DOPA oxidase staining, and abnormal karyotype were suggestive of malignant melanoma.

Serum gonadotropins and gonadal steroids associated with ovulation and egg production in sea turtles.

Changes in serum concentrations of gonadotropins and gonadal steroids during the periovulatory period were monitored in green, Chelonia mydas, and loggerhead, Caretta caretta, sea turtles. Turtles were from natural populations that nest on a coral island on the Great Barrier Reef. After nesting, each turtle was transferred to a holding tank and held for a maximum of 8 days.

Characterisation and distribution of epidermal growth factor receptors in equine hoof wall laminar tissue: comparison of normal horses and horses affected with chronic laminitis.

Epidermal growth factor (EGF) receptors were detected in plasma membrane preparations of equine hoof wall laminar tissue at concentrations comparable to that of equine liver. Scatchard analysis of the equilibrium binding data suggested the presence of two classes of EGF binding sites in most of the controls (plasma membranes from clinically normal horses); a high-affinity class and a more numerous low-affinity class. The dissociation constant of the low-affinity class of EGF-specific receptors (KD = 1 x 10(-9)M) is in reasonable agreement with other values established for the EGF receptor.

Estrogens influence the natural history of Sinclair swine cutaneous melanoma.

Initial results (Cancer Res., 48: 1708-1711, 1988) suggest that ovariectomy alters the proliferation of congenital exophytic melanoma in Sinclair swine. In order to provide a phenotypic basis for this effect, histopathological staging of 375 exophytic melanomas from 236 intact male and female Sinclair swine was compared with 114 lesions from 51 gonadectomized (6 weeks of age) and 90 lesions from castrated swine receiving s.

EGF receptor-binding activity in the urine of normal horses and horses affected by chronic laminitis.

A heterologous radioreceptor binding assay (RRA) has been developed capable of detecting nanogram amounts of epidermal growth factor (EGF) receptor-binding activity in equine urine. The binding parameters of [125I]mEGF (murine EGF) to EGF receptors on equine plasma membranes are in good agreement with values from other EGF-RRA systems. The dissociation constant estimated from equilibrium methods (KD = 4 X 10(-10) M) is in reasonable agreement with that determined from the rate constants (KD = 6 X 10(-10) M) and is in good agreement with values determined in other species.

Seasonal changes in serum gonadal steroids associated with migration, mating, and nesting in the loggerhead sea turtle (Caretta caretta).

Adult male loggerhead sea turtles, Caretta caretta, exhibited a "prenuptial" spermatogenic cycle that was coincident with increased concentrations of serum testosterone (T). Serum T was high during the months when migration and mating have been recorded for males. In contrast to females, males appear to be annual breeders.

Equine laminitis: a potential model of Raynaud's phenomenon.

Raynaud's phenomenon (RP) and equine laminitis in the horse are medical enigmas. Clinical and scientific data were compared to evaluate the degree of similarity that exists between these two peripheral vascular diseases. Data indicate that certain pathologic and pharmacologic aspects seem to have common features.

Comparative histopathology of porcine and human cutaneous melanoma.

Pigmented tumors resembling cutaneous melanoma were first reported in Sinclair miniature swine in 1967. Since that time, carefully planned breeding has established that this is an inherited malignancy the natural history of which mimics human cutaneous melanoma in a number of ways. Because of these characteristics, miniature swine melanoma appears to be an effective model with which to investigate the mechanisms influencing initiation, growth, and progression of human melanoma.

Serum testosterone and estradiol 17-beta concentrations in 15 dogs with perineal hernia.

Serum testosterone and estradiol 17-beta concentrations, and serum testosterone-to-estradiol ratio were evaluated in 15 dogs (greater than or equal to 5 years old) with perineal hernia (9 sexually intact males and 6 castrated males) and in 9 clinically normal sexually intact male dogs greater than or equal to 5 years old. There was no significant difference in serum testosterone-to-estradiol ratio between sexually intact male dogs with perineal hernia and clinically normal sexually intact male dogs. In castrated dogs with perineal hernia, serum testosterone concentration and testosterone-to-estradiol ratio were significantly (P less than 0.

Seasonal variation in serum testosterone, testicular measurements and semen characteristics in the collared peccary (Tayassu tajacu).

Blood samples and testicular measurements were obtained from 4-8 captive adult collared peccaries monthly for 18 months and from wild adult males during summer (N = 16) and winter (N = 22) seasons. Serum concentrations of testosterone were determined by radioimmunoassay. Semen samples were collected monthly by electroejaculation from captive males for 1 year.

Increased levels of arginine vasotocin and neurophysin during nesting in sea turtles.

Arginine vasotocin (AVT) and neurophysin (NP) levels were measured by radioimmunoassay in two species of sea turtle, the olive ridley, Lepidochelys olivacea, and the loggerhead, Caretta caretta, during the brief period of nesting and oviposition. In both species, AVT was low in animals which were not reproductively active. AVT was also low at the time animals emerged from the surf to nest, but increased significantly during oviposition and then declined as the animals returned to the water.