Suppression of prostaglandin F-2 alpha release and delay of luteolysis after active immunization against oxytocin in the goat

Active immunization against oxytocin significantly prolonged the oestrous cycle in 3 out of 4 goats; the mean (+/- s.e.m.) cycle length was 29.1 +/- 1.7 days (n = 12) compared to 19.4 +/- 0.6 days (n = 9) in control animals. During Days 10-21 of the cycle in the 3 responsive goats, peripheral plasma concentrations of progesterone and oxytocin were steady and those of 13,14-dihydro-15-keto-prostaglandin F-2 alpha were very low (50-100 pg X ml-1) with no marked pulsatile activity. The major effect of immunization would appear to be suppression of the synthesis of the uterine luteolysin PGF-2 alpha, thus confirming that endogenous oxytocin has a facilitatory role in luteolysis via prostaglandin production.     

Effects of calmodulin and lipoxygenase inhibitors on LH (lutropin)- and LHRH (luliberin)-agonist-stimulated steroidogenesis in rat Leydig cells.

The results of this study, carried out with purified rat Leydig cells, indicate that there are no major differences in the stimulating effects of lutropin (LH) and luliberin (LHRH) agonists on steroidogenesis via mechanisms that are dependent on Ca2+. This was demonstrated by using inhibitors of calmodulin and the lipoxygenase pathways of arachidonic acid metabolism. All three calmodulin inhibitors used (calmidazolium, trifluoperazine and chlorpromazine) were shown to block LH- and LHRH-agonist-stimulated steroidogenesis. This probably occurred at the step of cholesterol transport to the mitochondria. Similarly, three lipoxygenase inhibitors (nordihydroguaiaretic acid, BW755c and benoxaprofen), inhibited both LH- and LHRH-agonist-stimulated steroidogenesis. The amounts of the inhibitors required were similar for LH- and LHRH-agonist-stimulated steroidogenesis. Steroidogenesis stimulated by the Ca2+ ionophore A23187 was also inhibited, but higher concentrations of the inhibitors were required. Indomethacin (a cyclo-oxygenase inhibitor) increased LHRH-agonist-stimulated steroidogenesis;this is consistent with the role of the products of arachidonic acid metabolism via the alternative, lipoxygenase, pathway. The potentiation of LH-stimulated testosterone production by LHRH agonist was unaffected by indomethacin or by lipoxygenase inhibitors at concentrations that inhibited LH-stimulated testosterone production by 75-100%. It was not possible to eliminate a role of calmodulin in modulating the potentiation, although higher concentrations of the inhibitors were generally required to negate the potentiation than to inhibit LH- or LHRH-agonist-stimulated testosterone production.     

On the Trail of Atmospheric Mutagens and Carcinogens: A Combined Chemical/Microbiological Approach

Major ecological problems of our polluted troposphere includeairborne toxic chemicals, acid rain and photochemical smog,all three of which are now recognized as being closely relatedchemical phenomena. We also recognize that inorder to developcost-effective strategies for their control, which protect publichealth and the environment, there must be close scientific interactionsbetween chemists and biological scientists. For example, ofrapidly emerging importance is the development of risk assessmentevaluations for specific aspects of each of these problem areas.In preparing such assessments, chemists must define the "exposure,"and biological scientists the "effects." In this paper, I discuss an example of how such close interactionsproved indispensible in our search for atmospheric mutagensand carcinogens. Thus, an integrated chemical/ microbiologicalprocedure for the isolation and identificationof particulatechemical mutagens in respirable diesel soot and ambient particlesis described. Emphasis is placed on our use of the short-term,Ames Salmonella typhimurium bacterial mutagenicity test as arapid, and relatively inexpensive, means of following the biologicalactivities of these environmental mutagens through the chemicalsteps of their separation, isolation and identification fromhighly complex environmental samples. Possible mechanisms offormation of these particulate mutagens are discussed. Theyinclude the reactions of polycyclic aromatic hydrocarbons presenton the surfaces of combustion-generated particles with gaseousco-pollutants such as nitrogen dioxide plus nitric acid, andozone. In discussing this research on a societally "relevant" problem,we illustrate the importance of "Science as a Way of Knowing."We further suggest that this integrated approach to scientificproblem solving by chemical and biological scientists mightserve as an example of a discussion topic on human ecology forundergraduate courses in the natural sciences.     

Women doctors in urban general practice: the patients.

A large study from a representative sample of general practitioners in Manchester showed that women doctors saw more women patients than men doctors, especially in the childbearing age group. They saw a similar range of diagnoses as men doctors, though they saw more women patients for cervical smears, contraception, and breast disorders. Preventive health care may not be adequately provided for these in practices without a woman partner.     

An estimate of unique DNA sequence heterozygosity in the human genome

Summary Patients with recessive X-linked ichthyosis Patients with recessive X-linked ichthyosis (RXLI), one hereditary form of scaly skin, lack activity of the enzyme steroid sulfatase in all tissues studied. To investigate the molecular defect underlying the lack of enzyme activity, we prepared antisera against normal enzyme by injecting normal placental microsomal suspensions or partially purified steroid sulfatase into rabbits. Antibody activity was assessed by immunoprecipitation of detergent solubilized steroid sulfatase. In addition, we prepared rabbit antisera against RXLI placental microsomal suspensions. To detect immunologically cross-reactive material in patients' placentas, extracts were studied by immunoblot techniques and by competition with normal enzyme for antibody binding. Patients' extracts did not contain immunoreactive material co-migrating on electrophoresis with purified enzyme nor did they inhibit immunoprecipitation of normal enzyme. Sera from rabbits immunized with RXLI placental microsomes contain no antibodies to normal steroid sulfatase, as judged by their failure to immunoprecipitate normal enzyme or to react with normal steroid sulfatase on immunoblot. Thus the mutation in RXLI appears to reduce steroid sulfatase enzyme protein as well as enzyme activity. Portions of this material have appeared in abstract form in Clinical Research 31:564A, 1983 and 32:138A, 1984     

ESTIMATES OF CARRY-OVER EFFECTS IN TWO-PRODUCT HOME USAGE CONSUMER TESTS

In-house use consumer test data from four studies dealing with three pairs of household products and a pair of antiperspirant products were examined for significant carry-over (product usage order) effects, which would confound the analysis of treatment (product) effects. In each study, two products were compared using a two-period crossover design. One hundred twenty panelists participated in each study. A forced choice preference scale or a 9-point hedonic scale was used to obtain responses from various sensory attributes. In all studies, the estimates of carry-over effects were not significant at the 5% level. Transformation of hedonic scale data into preference dichotomy also gave estimates of carry-over effects which were not significant at the 5% level, but led to a loss of test sensitivity for detecting treatment differences. The authors recommend that all comparative crossover design studies in sensory evaluation be monitored for carry-over effects and that statistically determined sample size should be used to reduce the possibility of obtaining significant carry-over effects.     

The differential effect of 2-deoxyguanosine on concanavalin A-induced suppressor and cytotoxic activity

The effect of 2-deoxyguanosine (dGuo) on the generation in vitro of nonspecific suppressor cells in murine spleen cell cultures by concanavalin A (Con A) is examined. The experiments indicate that dGuo abrogates the generation of nonspecific suppressor activity by lectin stimulation of murine spleen cells. When comparisons were made between the effect of this nucleoside on the generation of suppressor and cytotoxic cells by Con A stimulation of murine spleen cells, it was found that dGuo only affected the generation of suppressor cells. The development of lectin-stimulated cytotoxicity was not affected by dGuo. In addition it was found that dGuo does not affect the NK activity of murine spleens.     

Stimulation of cholesterol side-chain cleavage by a luteinizing-hormone-releasing hormone (luliberin) agonist (ICI 118630) in rat Leydig cells.

The action of a luliberin (luteinizing-hormone-releasing hormone) agonist (ICI 118630) and lutropin (luteinizing hormone) on the activity of the cytochrome P-450 cholesterol side-chain cleavage enzyme in rat Leydig cells has been investigated. This has been carried out by studying the metabolism of exogenous (22R)-22- and 25-hydroxycholesterol to testosterone. It was found that both hydroxycholesterols increased testosterone production to higher levels than achieved by lutropin alone. Addition of luliberin agonist but not lutropin was found to increase further the metabolism of the hydroxycholesterol to testosterone; this occurred in the presence of saturating and subsaturating levels of the hydroxycholesterols. This effect of luliberin agonist was potentiated in the presence of lutropin. The protein synthesis inhibitor, cycloheximide, inhibited the luliberin agonist-induced stimulation of the hydroxycholesterol metabolism. At low calcium levels (1.1 microM), testosterone production was increased by addition of (22R)-22-hydroxycholesterol but the luliberin agonist effect was negated. The calmodulin inhibitor trifluoperazine inhibited (22R)-22-hydroxycholesterol-stimulated steroidogenesis and negated the luliberin agonist effect. These results indicate that luliberin agonist specifically increases the synthesis of the cytochrome P-450 cholesterol side-chain cleavage enzyme in rat testis Leydig cells.     

Analysis of a model of a vertically transmitted disease

A model is presented of a disease that can be transmitted directly from parent to offspring (vertical transmission) as well as through contact with infectives. A global stability analysis is given for the basic model and the epidemiological effects of vertical transmission are discussed. The effects of the addition of maturation and incubation delays as well as spatial diffusion are analyzed in some special cases.     

Ontogeny of the Behavior of Strombus maculatus (Gastropoda: Strombidae)

The ontogeny of strombid behavior was studied by observing thebehavior of Strombus maculatus veligers collected from the planktonand reared past metamorphosis to adults, and by observing juvenilestrombids collected in the field. Complete adult modal actionpatterns (MAP's) associated with locomotion, feeding, and rightingof overturned shells are performed by S. maculatus juvenilesimmediately after metamorphosis. There are changes in the frequencyof the use of certain MAP's which are associated with variationsin shell shape and size. The unique strombid escape response to molluscivorous gastropods(Conns spp.) is not released until juvenile S. maculatus arethree weeks past metamorphosis and two millimeters in shelllength. At that stage, the complete response is released uponthe first encounter with a predator. Experience with a predatordoes not seem to lower the age or size criteria. During ontogeny there is a trend toward an increasing complexityof behavior which is paralleled by an increasing complexityof neural structure and general morphology. There are majorsteps in the ontogeny of strombid behavior which probably coincidewith neural and morphological stages.