Cadmium and platinum suppression of erythropoietin production in cell culture: clinical implications.

Both toxic exposure to cadmium and cancer therapy with cisplatin (CDDP) can induce anemia in patients owing to the insufficient production of erythropoietin (EPO). Therefore, the effects of cadmium chloride (Cd) and CDDP in the Hep3B human hepatoma cell line, which up-regulates EPO expression in response to hypoxia and cobalt (Co), were investigated. The induction of binding activity of the HIF-1 transcription factor and EPO mRNA expression and protein production were suppressed by Cd and CDDP in a dose-dependent manner with no apparent cell damage. Mercuric chloride also suppressed hypoxia- and Co-induced EPO production, mRNA expression, and HIF-1 binding in a manner similar to Cd and CDDP, whereas zinc chloride suppressed Co-induced EPO production, mRNA expression, and HIF-1 binding but did not affect hypoxia induction or that observed after simultaneous exposure to hypoxia and Co. In contrast, lead and tin salts had no effect on HIF-1 activation or EPO expression. These results indicate that Cd and CDDP have a strong and specific inhibitory effect on hypoxia- and Co-induced signaling and EPO induction in hepatic cells. It is likely that these agents cause anemia by directly impacting EPO production in the kidney. (Blood. 2000;96:3743-3747)

Targeted mutagenesis by duplication insertion in the radioresistant bacterium Deinococcus radiodurans: radiation sensitivities of catalase (katA) and superoxide dismutase (sodA) mutants.

Deinococcus radiodurans R1 is extremely resistant to both oxidative stress and ionizing radiation. A simple and general targeted mutagenesis method was developed to generate catalase (katA) and superoxide dismutase (sodA) mutants. Both mutants were shown to be more sensitive to ionizing radiation than the wild type.

Molecular aspects of malignant melanoma. Role of protooncogenes and oncosuppressor genes.

This review summarizes current knowledge of oncogenes and tumour-suppressor genes in development and progression of malignant melanoma.

Possible induction by estrous cows of pheromone production in penmates.

The primary attractive odors of estrous cows apparently induced production of secondary attractive odors in penmates. Presence of both odors was reflected by the bull's olfactory behavior. The inducing effect was strongest on the day of estrus and the day before. The information content of the primary and secondary odors was different since a sexually experienced bull was able to distinguish olfactorily between estrous and nonestrous cows. The secondary odors attracted at least transient bull's interest, resulting in sniffing, urine tasting, and flehmen reactions, but not mounting attempts. The induced production of attractive odors and lack of precise smell discrimination in penmates may lead to erroneous detection of estrus in cows and heifers that show false estrous signs without corresponding changes in their reproductive organs. Similar factors may be involved in triggering mounting among feedlot steers (buller steer syndrome).

Histology of a heifer placentome after interspecies transfer of a gaur embryo.

Histological examination of a single placentome recovered from a Holstein heifer (Bos taurus ) after delivery of a dead 9.5-mo-old gaur (Bos gaurus ) calf revealed failure of proper development of the chorioallantoic villi after interspecies embryo transfer. Macroscopically, the placentome appeared normal in size, its surface was rough, and on crosssection, the penetration of the villi was irregular and very different from the homogeneous penetration in developed cow placentomes. Microscopically, the heifer caruncle had an extensive system of maternal crypts but the villi failed to branch completely and entered only about one half of the available crypt spaces. The epithelial lining of the maternal crypts in the heifer placentome was nearly missing, which was rather unusual for a species of the genus Bos . The overall picture suggested a decreased feto-maternal compatibility, resulting in poor development of the utero-placental contact, retarded fetal growth, and ultimate fetal death.

Comparative development of ruminant placentomes.

Histological examination of placentomes from cows, sheep, deer, and several antelope species revealed a common pattern of development of the utero-placental junction. Chorionic membrane in contact with the uterine caruncles developed "milky patches" composed of a thick trophoblastic epithelium and multiple allantoic blood vessels, while caruncles formed simultaneously a network of crypts. The milky patches formed chorioallantoic villi that penetrated into the caruncular crypts usually simultaneously with both the villi and crypt formation but partial delay between the villi/crypt formation and penetration had no apparent detrimental effect on the fetus. The villi penetrated into caruncles in a row until they reached the dense basal layer separating caruncular mass from adjacent glandular endometrium. Further placentome growth continued by increasing the length, diameter, branching, and surface corrugation of the villi. Placentomes in different stages of development coexisted at different locations within the uterus throughout the pregnancy. During placental release after parturition, entire villi or only the villi mainstems can pull out of the maternal crypts, or the entire placentome mass can separate from the uterine wall. The remaining maternal portions of the placentomes are destroyed and sloughed down to the basal layer, leaving only a narrow band of the caruncular tissue for the regeneration of caruncles. The bare, wrinkled caruncular surface is then covered with a new epithelium and ultimately becomes smooth.

Comparative histology of antelope placentomes.

The histological structure of ruminant (family: Bovidae) placentomes in eight antelope species was compared to that of domestic cattle and sheep. The chorioallantoic villi differed in degree of branching, surface corrugation, and complexity of utero-placental junction. All species had the epitheliochorial type of placenta, with the epithelial lining of maternal caruncular crypts varying between cellular and syncytial types. Uganda kob (Kobus kob, Reduncinae) and common duiker (Sylvicapra grimmia, Cephalophinae) had the simplest structures with minimal villous branching, round to polygonal villous cross-sections, and cellular crypt lining. Common eland (Taurotragus oryx, Tragelaphinae) and greater kudu (Tragelaphus strepsiceros, Tragelaphinae) had moderate villous branching, polygonal to mildly corrugated villous cross-sections, and cellular crypt lining with slight signs of syncytium. Wildebeest (gnu, Connochaetes gnou, Alcelaphinae) and sable antelope (Hippotragus niger, Hippotraginae) had moderate villous branching with corrugated surface and almost completely syncytial crypt lining. Steenbok (Raphicerus campestris, Neotraginae) and impala (Aepyceros melampus, Aepycerotinae) had the most complicated branching of villi and corrugation, and their crypt lining was clearly syncytial. Cattle (Bos taurus) and sheep (Ovis aries) had villous branching and corrugation similar to impala, and their crypt lining resembled that of eland and impala, respectively.

Implications of the placental structure compatibility for interspecies embryo transfer.

Comparative histological features of the chorionic villi in placental cotyledons of the common eland (Taurotragus oryx ) and bongo (Boocercus euryceros ) antelopes and okapi (Okapia johnstoni ) and giraffe (Giraffa camelopardalis ) were examined. The chorionic villi in both antelope species showed only moderate branching and/or surface corrugation and their cross-sections were polygonal to oval. The close similarity in the structure of cotyledons has been apparently a contributing factor for success in mutual interspecies embryo transfer. The chorionic villi in okapi and giraffe had very different structures. In okapi the villi on cross-section were round and filled with thin connective tissue. They showed minimal branching and surface corrugation. In giraffe the villi showed extensive surface corrugation, had multiple fine branches, and were filled with a more dense connective tissue. Prospect for materno-fetal compatibility in mutual embryo transfer between these species is guarded.

Volatile fatty acids in urine and vaginal secretions of cows during reproductive cycle.

Levels of volatile fatty acids (VFA) in vaginal secretions (VS) of cows were nearly independent of concentration changes of acids in the gastrointestinal tract, while levels in urine showed marked dependence. During three-week cycles, the VFA concentrations in VS increased shortly before heat and decreased to one third on days 19-22. Some cows showed an immediate increase after heat while in others the increase was slow and gradual. Moderately increased levels at midcycle were probably related to interovulatory follicle growth. Content of VFA in VS of pregnant cows was significantly above the level of the postestrus drop. Some pregnant cows in the first two thirds of gravidity had substantially higher levels of VFA than the other cows. Changes in VFA levels have a potential value for estrus detection and pregnancy diagnosis in cows. The gas chromatographic method used is too slow and tedious for practical application, but a reliable semiquantitative test for rapid proof of VFA or acetic acid in VS would be a very useful device for field use. It would have a substantial impact on the economy of cattle production by minimizing the loss of time due to delayed breeding.

Possible pheromonal regulation of reproduction in wild carnivores.

Recent observations of social behavior and reproduction in wolves, coyotes, hunting dogs, mongooses, and lions suggest possible involvement of pheromones in the regulation of reproductive activity. Observed phenomena resemble the known pheromonal effects in mice such as suppression or synchronization of estrus, induction of maternal behavior, and interruption of pregnancy. Further studies are necessary to verify the supposed biological effects of carnivore pheromones and to determine their chemical nature.

Separation of human and animal cells by steric field-flow fractionation.

In this work, the feasibility of separating and characterizing cell populations by steric field-flow fractionation (steric FFF) is demonstrated by application to fixed human and avian red cells, fresh blood from several species, and viable HeLa cells. The basis for this work is established by means of a discussion of the role of steric FFF in the broad family of field-flow fractionation techniques. The behavior of steric FFF is then characterized by application to standard polystyrene latex beads and to fixed red blood cells. Studies of these standards and of the other cells noted under various conditions of field strength and flow velocity are used to improve the separation conditions and approach optimization. It is shown that the fixed human and avian red cells can be separated in a time of less than 15 min. In addition, it is shown that HeLa cells maintain their viability after passage through the separation channel.

Clinical evaluation of ketone bodies in body fluids of cows in late pregnancy and their fetuses.

Ketone body concentrations were determined in six body fluids of cows in late pregnancy and their fetuses (blood plasma and urine of cows, amniotic and allantoic fetal fluids, and fetal blood serum and urine) using the head-space gas chromatographic method. Physiological ratios O/T% of oxidized (acetone and acetoacetic acid) to total (acetone, isopropanol, acetoacetic and 3-hydroxybutyric acid) ketone bodies were below 10% in cow blood plasma and urine, fetal serum and urine, and allantoic fluid, and below 20% in amniotic fluid. A scheme for the evaluation of the degree and duration of ketosis based on the O/T% ratio is proposed. The existence of a renal regulatory mechanism for excretion of ketone bodies is suggested by analogy with the renal acidobasic regulation.

Some uterine parameters in antelopes and a giraffe.

Uteri of 69 African antelopes and a giraffe were morphologically examined and numbers of caruncles and their rows in each horn were recorded. Antelopes of subfamilies Taurotraginae, Aepycerotinae, Antilopinae, and Alcelaphinae had about 50 to 100 caruncles arranged in four rows in each uterine horn. Hippotraginae had about 100 to 200 caruncles in six to eight rows in each horn, and Reduncinae had about 10 to 20 caruncles in two rows in each uterine horn. The giraffe had about 70 caruncles arranged in four rows in each uterine horn. Uterine caruncles in some antelopes had specific features such as pigmentation of apices, caruncles on stems, and caruncles with honeycomb structure.