Peroxisome proliferator-activated receptor alpha in the human breast cancer cell lines MCF-7 and MDA-MB-231

Peroxisome proliferator-activated receptor (PPAR) alpha is a ligand-activated transcription factor that has been linked with rodent hepatocarcinogenesis. It has been suggested that PPARalpha mRNA expression levels are an important determinant of rodent hepatic tumorigenicity. Previous work in rat mammary gland epithelial cells showed significantly increased PPARalpha mRNA expression in carcinomas, suggesting the possible role of this isoform in rodent mammary gland carcinogenesis. In this study we sought to determine whether PPARalpha is expressed and dynamically regulated in human breast cancer MCF-7 and MDA-MB-231 cells. Having established the presence of PPARalpha in both cell types, we then examined the consequence of PPARa activation, by its ligands Wy-14,643 and clofibrate, on proliferation. With real-time reverse transcriptase-polymerase chain reaction, we showed that PPARalpha mRNA was dynamically regulated in MDA-MB-231 cells and that PPARalpha activation significantly increased proliferation of the cell line. In contrast, PPARalpha expression in MCF-7 cells did not change with proliferation during culture and was present at significantly lower levels than in MDA-MB-231 cells. However, PPARalpha ligand activation still significantly increased the proliferation of MCF-7 cells. The promotion of proliferation in breast cancer cell lines following PPARalpha activation was in stark contrast to the effects of PPARgamma-activating ligands that decrease proliferation in human breast cancer cells. our results established the presence of PPARalpha in human breast cancer cell lines and showed for the first time that activation of PPARalpha in human breast cancer cells promoted proliferation. Hence, this pathway may be significant in mammary gland tumorigenesis. (C) 2002 Wiley-Liss, Inc.

Induction of birth in the bandicoot (Isoodon macrourus) with prostaglandin and oxytocin

As in eutherians, maturation of the fetal pituitary and adrenal glands together with an increase in prostaglandin and mesotocin or oxytocin production initiates birth in marsupials. in this study, prostaglandin (Lutalyse) or oxytocin (Syntocinon) were administered to pregnant bandicoots at 05:00 h on the calculated day of birth and the resultant effects were filmed for analysis. The administration of prostaglandin caused the bandicoot to adopt the birth position several minutes after injection (n = 2). However, the bandicoot did not give birth for several hours. Birth occurred at a similar time of day to that observed for untreated bandicoots (n = 7), between 08:00 h and 12:00 h. After an injection of oxytocin, the bandicoot assumed the birth position and birth occurred within several minutes. The young were alive while still connected to their allantoic stalks. However, they were unable to attach to the teats and did not survive (n = 4). The induced young were the colour of venous blood and died soon after the umbilicus was separated, indicating that the cardiopulmonary system of these neonates was underdeveloped and inadequate to maintain life. The results from this study demonstrate that prostaglandin is required to prepare the bandicoot for birth, and mesotocin is required for contraction of the uterus and for birth to occur.

A case of myoepithelial carcinoma displaying biallelic inactivation of the tumour suppressor gene APC in a patient with familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by mutation of the APC gene. It is characterised by the appearance of hundreds to thousands of colorectal adenomas in adolescence and the subsequent development of colorectal cancer. Various extracolonic malignancies are associated with FAP, including desmoids and neoplasms of the stomach, duodenum, pancreas, liver, and brain. We present a family affected by FAP with an exon 14 APC mutation displaying two rare extracolonic lesions, a hepatoblastoma and a myoepithelial carcinoma. The hepatoblastoma was found in a male patient aged 2 years. The second lesion, a myoepithelial carcinoma of the right cheek, was found in a female patient aged 14 years. Inactivation of the normal APC allele was demonstrated in this lesion by loss of heterozygosity analysis, thus implicating APC in the initiation or progression of this neoplasm. This is the first reported case of this lesion in a family affected by FAP.

Enhancement or modulation of the vector competence of ochlerotatus vigilax (Diptera : Culicidae) for Ross River virus by temperature

Two different doses of Ross River virus (1111) were fed to Ochlerotatus vigilax (Skuse), the primary coastal vector in Australia; and blood engorged females were held at different temperatures up to 35 d. After ingesting 10(4.3) CCID50/Mosquito, mosquitoes reared at 18 and 25degreesC (and held at the same temperature) had higher body remnant and head and salivary gland titers than those held at 32degreesC, although infection rates were comparable. At 18, 25, and 32degreesC, respectively, virus was first detected in the salivary glands on days 3, 2, and 3. Based on a previously demonstrated 98.7% concordance between salivary gland infection and transmission, the extrinsic incubation periods were estimated as 5, 4, and 3 d, respectively, for these three temperatures. When Oc. vigilax reared at 18, 25, or 32degreesC were fed a lower dosage of 10(3.3) CCID50 RR/mosquito, and assayed after 7 d extrinsic incubation at these (or combinations of these) temperatures, infection rates and titers were similar. However, by 14 d, infection rates and titers of those reared and held at 18 and 32degreesC were significantly higher and lower, respectively. However, this process was reversible when the moderate 25degreesC was involved, and intermediate infection rates and titers resulted. These data indicate that for the strains of RR and Oc. vigilax used, rearing temperature is unimportant to vector competence in the field, and that ambient temperature variations will modulate or enhance detectable infection rates only after 7 d: extrinsic incubation. Because of the short duration of extrinsic incubation, however, this will do little to influence RR epidemiology, because by this time some Oc. vigilax could be seeking their third blood meal, the latter two being infectious.

NPS-2143 - Treatment of osteoporosis - Calcilytic

Efforts to discover new treatments for osteoporosis led to the identification of the potent and selective, small-molecule calcium receptor antagonist NPS-2143. NPS-2143 is the prototype calcilytic drug, designed to act on calcium receptors on the surface of parathyroid glands, stimulating the release of the body's own stores of native parathyroid hormone (PTH). In osteopenic ovariectomized rats, daily oral administration of NPS-2143 resulted in moderate but sustained increases in plasma PTH levels and marked increases in bone formation and resorption, with no net bone gain or loss. The combination of NPS-2143 and estrogen increases bone formation and density to a greater extent than either agent alone. These results suggest that NPS-2143 may be useful in the treatment of established osteoporosis.

Role of PGF(2 alpha) and oxytocin in parturition in the brushtail possum (Trichosurus vulpecula)

Maturation of the fetal pituitary and adrenal glands allows the secretion of cortisol, which in turn leads to an increase in prostaglandin and mesotocin production. The production of prostaglandin and mesotocin results in an increase in uterine contractions and initiates birth in marsupials. The major metabolite of PGF(2alpha), 13,14-dihydro-15-keto-prostaglandin F-2alpha (PGFM), has been found in the plasma of the possum at the time of birth and administration of PGF(2alpha) to female possums induced the adoption of the birth position. Evidence that mesotocin is an integral hormone of birth in the tammar wallaby indicates that both PGF(2alpha) and mesotocin or oxytocin are required for marsupial birth. The presence of PGF(2alpha) receptors in the uterus and corpus luteum of the possum, and the in vitro uterine responsiveness to PGF(2alpha) or oxytocin, were examined. PGF(2alpha) receptors were not observed in possum uteri and the inability of PGF(2alpha) to cause contractions indicates that PGF(2alpha) is not involved directly in contraction of the uterus at parturition. The presence of oxytocin and mesotocin receptors in the uterus of possoms and the ability of oxytocin to induce uterine contraction in vitro supports the view that mesotocin is required for expulsion of the young from the uterus. Low numbers of PGF(2alpha) receptors were found in the possum corpus luteum at birth, indicating an involvement of PGF(2alpha) in regression of the corpus luteum.

Skin toxins and external parasitism of coral-dwelling gobies

Toxic (Gobiodon spp.) and non-toxic (Paragobiodon xanthosomus) gobies became infected with external parasites (gnathiid isopods) at equal rates in a laboratory experiment. Parasites were evenly distributed over the body of P. xanthosomus but were mostly confined to the fins of Gobiodon spp., where toxin glands are less abundant. Skin toxins were not associated with the rate of infection but their distribution did appear to influence the site of parasite attachment. (C) 2003 The Fisheries Society of the British Isles.

Structure of the gut contents of Trichogramma australicum Girault (Hymenoptera : Trichogrammatidae) larvae fixed in situ in eggs of its host Helicoverpa armigera (Hubner) (Lepidoptera : Noctuidae)

Trichogramma australicum larvae develop most rapidly in younger eggs of its host, the pest lepidopteran Helicoverpa armigera . To establish how the developmental stage of the host affects the diet of T. australicum , larvae were fixed in situ in eggs of H. armigera of different ages and the structure of the egg contents and parasitoid gut contents examined histologically. Larvae feeding on newly laid host eggs contain primarily yolk particles in their gut, while larvae feeding on older hosts contain necrotic cells and yolk particles. The gut of T. australicum larvae does not contain organised tissue remnants, indicating that larvae feed primarily by sucking food into their pharynx and feed best on a mixture of particulate semisolids in a liquid matrix. Secretory structures of T. australicum larvae that could be involved in modifying the host environment were examined. The hindgut is modified to form an anal vesicle with a number of attributes suggesting that it may be a specialised secretory structure. The paired salivary glands open to the exterior via a common duct.

The ultrastructure and function of the silk-producing basitarsus in the Hilarini (Diptera : Ernpididae)

The tribe Hilarini (Diptera: Empididae), commonly known as dance flies, can be recognised by their swollen silk-producing prothoracic basitarsus, a male secondary sexual characteristic. The ultrastructure and function of the silk-producing basitarsus from one undescribed morphospecies of Hilarini, 'Hilarempis 20', is presented. Male H. 20 collect small parcels of diatomaceous algae from the surface of freshwater creeks that they bind with silk produced by the gland in the basitarsus. The gift is then presented to females in a nearby swarm, composed predominately of females. The basitarsus houses approximately 12 pairs of class III dermal glandular units that congregate on the ventral side of the cavity. Each gland cell has a large extracellular lumen where secretion accumulates. The lumen drains to the outside via a conducting canal encompassed by a canal cell and a duct extending through the shaft of a specialised secretory spine. The secretory spines lie in pairs in a ventral groove that runs the length of the basitarsus. A comparison of the basitarsal secretory spines with sensilla on the basitarsi of non gland-bearing legs of males, and with non gland-bearing prothoracic. basitarsi of females, suggests that the glandular units are derived from contact chemosensory sensilla. (C) 2003 Elsevier Ltd. All rights reserved.