Effect of prostaglandins A1, A2, B1, B2, E2 and F2 alpha on human umbilical cord vessels

Human umbilical blood vessels have the ability to close spontaneously following delivery at term. It has been suggested that prostaglandins may have a possible physiological role in its closure. This study investigates the effects of 6 naturally occurring prostaglandins (A1, A2, B1, B2, E2, F2a) on the umbilical blood vessels. Umbilical cords were collected from cases of normal spontaneous vaginal deliveries and cesarian section at term. A total of 41 strips of umbilical arteries and 26 strips of umbilical veins from 24 cords were used. A 4-point bioassay method was used to compare the potency of prostaglandins A1, A2, B1 and F2a with PGE2. The effect of Polyphloretin Phosphate (PPP) on prostaglandin-induced contractions was studied on umbilical artery strips from 12 cords. The 6 prostaglandins exerted a stimulant effect on the isolated strips of human umbilical arteries. Prostaglandin B2 was the most potent compound on the umbilical vein, followed by PGA2. PPP in the concentration range of 10 to 40 mcg/ml completely eliminated the responses of PGE2, F2a, A1, A2, and B1. Responses to PGB2 were considerably but not completely abolished. PPP (up to 40 mcg/ml) did not affect contractions induced by 5-hydroxytryptamine, suggesting the presence of discrete receptor sites in the blood vessels for different pharmacologically active compounds. This is the first report of the constrictor effect of PGA and PGB compounds. These naturally occuring prostaglandins with high potencies (compared with other prostaglandins and other vasoactive substances) may play a role in spontaneous closure of umbilical vessels. PGE1, E2, F1 and F2a are found in umbilical blood vessels obtained at term.     

Comparison of the effects of prostaglandins F1alpha, F2alpha, F1beta, and F2beta on the canine pulmonary vascular bed.

The effects of four F series prostaglandins on the pulmonary vascular bed were compared under conditions of controlled pulmonary blood flow in the intact spontaneously breathing dog. PGF1alpha and PGF2alpha increased lobar arterial pressure whereas PGF1beta and PGF2beta had little if any effect when infused into the lobar artery. The increase in lobar arterial pressure in response to PGF1alpha and PGF2alpha was associated with a significant increase in lobar venous pressure but no change in left atrial pressure. These data indicate that PGF1alpha and PGF2alpha increase pulmonary vascular resistance by constricting lobar veins and vessels upstream to small veins, presumed to be small arteries. It is concluded that in the pulmonary vascular bed the configuration of the hydroxyl group at carbon 9 is an important determinant of pressor activity.     

Proton Magnetic Resonance Studies of the Interactions of Histones F1 and F2B with DNA

THE determination of sequences of histones F2A1(refs. 1 and 2) and F2B (ref. 3) and the amino-acid compositions of peptides of histone F1 (ref. 4) has shown that the distribution of residues along the polypeptide chains is extremely irregular. In particular, different regions of the molecule have markedly different characters. Thus the amino half of F2A1 has a ratio of basic to acidic residues of 15.6: 1 while for the carboxyl half of the molecule it is 1.5 : 1; for F2B this ratio is 13 : 1 for the amino quarter of the molecule and 1.9: 1 for the remainder. In the case of F1 this “polarity” is reversed: the carboxyl half of the molecule has a ratio of basic to acidic residues of 15 : 1, the amino half of 1.2 : 1. Further, regions rich in basic residues also contain a high proportion of helix destabilizing residues, proline in F1 and F2B and glycine in F2A1. In contrast, the non-basic regions contain a higher proportion of the apolar residues regarded as helix stabilizers and higher proportions of acidics, aromatics and threonine and serine residues. The characterization of two different regions led to the suggestion^1–4 that the basic regions of the polypeptide chains are the primary sites of interaction with DNA, while the non-basic regions have the potential for the formation of definite conformations and might be involved in specific interactions other than with DNA.     

Thromboxane B2, 6-keto-prostaglandin F1 alpha, and prostaglandin F2 alpha production by contracting pregnant rate uteri in vitro

While prostaglandin production by uterine tissue has been shown to be involved in the contractile mechanism of this tissue, less attention has focused upon the involvement of other prostanoids. We have simultaneously measured in vitro isometric contractility of pregnant rat uteri with the release of prostaglandin F2 alpha (PGF), 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha) and thromboxane B2 (TXB2) into the bathing medium under various conditions. Frequency of uterine contractions and integrated contractile force (ICF) increased from 15 days of gestation and peaked at the time of parturition. Activity was generally greatest during the first 15 min of incubation except during parturition and on Day 1 postpartum when the uterine segment remained active for 1 h experimental period. Indomethacin (INDO) significantly reduced contractile activity regardless of gestational stage. PGF, TXB2, and 6-k-PGF1 alpha increased with gestational age, peaking at the time of parturition. Production was greatest during the first 15 min of incubation and INDO inhibited production of each prostanoid regardless of gestational stage. Imidazole (100 micrograms/ml) inhibited TXB2 production without affecting PGF or 6-k-PGF1 alpha levels. Frequency of contraction and ICF were not affected by imidazole treatment despite TXB2 reduction. These data demonstrate that the in vitro uterus from pregnant rats is capable of producing prostanoids other than prostaglandins and their production generally parallels uterine contractile activity. Thus, the possibility that these prostanoids are involved in physiologic changes during parturition warrants further investigation.     

Epistatic gene effects on the yield of the parents of F1, F2, BC1 and BC2 progeny

The genetic analysis of 5 tomato hybrids (Danubius F₁, Luna F₁, Lido F₁, Balkan F₁ and Mi-10 F₁) was made. We produced their F₁, F₂, BC₁ and BC₂ generations and analysed their yield (on the first three flower branches) as well as some of the yield components of tomato fruits (mean fruit weight, mean fruit weight on the first flower branch, fruit length, fruit width, and number of locules). In order to estimate the gene effects, we applied the additive-dominance mode with three and six parameters. Epistatic gene effects were estimated by applying the six-parameter mode (Mather and Jinks 1982). As for yield and yield components, there were significant differences between the mean values of parents and their progeny. On the basis of the investigated genetic parameters, the obtained results suggested that the additive and dominance gene effects prevailed in the yield and yield components (Danubius F₁, Luna F₁, Lido F₁, Mi-10 F₁), whereas epistatic gene effects were excluded. As for the hybrid Balkan F₁, we recorded significant gene effects, both the additive and the dominance ones in the yield inheritance: additive x additive and dominance x dominance (with the negative sign). The estimated values of the epistatic gene effects were the most prominent in inheriting the feature average fruit weight on the first flower branch — additive x dominance gene effects. They represented the most frequent type of the interallele interaction recorded in the investigated hybrids.     

Biosynthetic relationship among aflatoxins B1, B2, M1, and M2

Aflatoxins are a family of toxic, acetate-derived decaketides that arise biosynthetically through polyhydroxyanthraquinone intermediates. Most studies have assumed that aflatoxin B1 is the biosynthetic precursor of the other aflatoxins. We used a strain of Aspergillus flavus which accumulates aflatoxin B2 to investigate the later stages of aflatoxin biosynthesis. This strain produced aflatoxins B2 and M2 but no detectable aflatoxin B1 when grown over 12 days in a low-salt, defined growth medium containing asparagine. Addition of dichlorvos to this growth medium inhibited aflatoxin production with concomitant accumulation of versiconal hemiacetal acetate. When mycelial pellets were grown for 24, 48, and 72 h in growth medium and then transferred to a replacement medium, only aflatoxin B2 and M2 were recovered after 96 h of incubation. Addition of sterigmatocystin to the replacement medium led to the recovery of higher levels of aflatoxins B2 and M2 than were detected in control cultures, as well as to the formation of aflatoxins B1 and M1 and O-methylsterigmatocystin. These results support the hypothesis that aflatoxins B1 and B2 can arise independently via a branched pathway.     

利用回交B1和B2及F2群体鉴定数量性状两对主基因+多基因混合遗传模型

ＱＴＬ作图和主基因＋多基因混合遗传分析表明：拓展两对基基因＋多基因混合遗传模型十分必要。本文利用混合分布理论,ＡＩＣ准则在回交Ｂ１和Ｂ２群体或Ｆ２群体中鉴定两对主基因的存在,当主基因存在时估计其遗传参数;同时还改进了利用亲本,Ｆ１和回交Ｂ１和Ｂ２群体,或亲本,Ｆ１和Ｆ２群体鉴定多基因存在的方法,分布参数的估计采用ＩＥＣＭ算法,以水稻株高性状为例说明该方法的应用。     

Biosynthetic relationship among aflatoxins B1, B2, G1, and G2

Aspergillus parasiticus NIAH-26, a UV-irradiated mutant of A. parasiticus SYS-4 (NRRL 2999), produces neither aflatoxins nor precursors. When sterigmatocystin (ST) or O-methylsterigmatocystin was fed to this mutant in YES medium, aflatoxins B1 (AFB1) and G1 (AFG1) were produced. When dihydrosterigmatocystin (DHST) or dihydro-O-methylsterigmatocystin was fed to this mold, aflatoxins B2 (AFB2) and G2 (AFG2) were produced. The reactions from ST to AFB1 and DHST to AFB2 were also observed in the cell-free system and were catalyzed stepwise by the methyltransferase and oxidoreductase enzymes. In the feeding experiments of strain NIAH-26, the convertibility from ST to AFB1-AFG1 was found to be remarkably suppressed by the coexistence of DHST in the medium, and the convertibility from DHST to AFB2-AFG2 was also suppressed by the presence of ST. When some other mutants which endogenously produce a small amount of aflatoxins (mainly AFB1 and AFG1) were cultured with DHST, the amounts of AFB1 and AFG1 produced were significantly decreased, whereas AFB2 and AFG2 were newly produced. In similar feeding experiments in which 27 kinds of mutants including these mutants were used, most of the mutants which were able to convert exogenous ST to AFB1-AFG1 were also found to convert exogenous DHST to AFB2-AFG2. These results suggest that the same enzymes may be involved in the both biosynthetic pathways from ST to AFB1-AFG1 and DHST to AFB2-AFG2. The reactions described herein were not observed when the molds had been cultured in the YEP medium.     

Biosynthetic relationship among aflatoxins B1, B2, G1, and G2.

Aspergillus parasiticus NIAH-26, a UV-irradiated mutant of A. parasiticus SYS-4 (NRRL 2999), produces neither aflatoxins nor precursors. When sterigmatocystin (ST) or O-methylsterigmatocystin was fed to this mutant in YES medium, aflatoxins B1 (AFB1) and G1 (AFG1) were produced. When dihydrosterigmatocystin (DHST) or dihydro-O-methylsterigmatocystin was fed to this mold, aflatoxins B2 (AFB2) and G2 (AFG2) were produced. The reactions from ST to AFB1 and DHST to AFB2 were also observed in the cell-free system and were catalyzed stepwise by the methyltransferase and oxidoreductase enzymes. In the feeding experiments of strain NIAH-26, the convertibility from ST to AFB1-AFG1 was found to be remarkably suppressed by the coexistence of DHST in the medium, and the convertibility from DHST to AFB2-AFG2 was also suppressed by the presence of ST. When some other mutants which endogenously produce a small amount of aflatoxins (mainly AFB1 and AFG1) were cultured with DHST, the amounts of AFB1 and AFG1 produced were significantly decreased, whereas AFB2 and AFG2 were newly produced. In similar feeding experiments in which 27 kinds of mutants including these mutants were used, most of the mutants which were able to convert exogenous ST to AFB1-AFG1 were also found to convert exogenous DHST to AFB2-AFG2. These results suggest that the same enzymes may be involved in the both biosynthetic pathways from ST to AFB1-AFG1 and DHST to AFB2-AFG2. The reactions described herein were not observed when the molds had been cultured in the YEP medium.     

Isolation of Novel Antifungal Antibiotics,Ezomycins A1, A2, B1 and B2

From ezomycin complex produced by a strain of Streptomyces were isolated four components named ezomycins A₁ (C₂₆H₄₀N₈O₁₆S), A₂ (C₁₉H₂₈N₆O₁₃), B₁ (C₂₆H₃₉N₇O₁₇S) and B₂ (C₁₉H₂₇N₅O₁₄) which are new pyrimidine nucleosides. Ezomycins A₁ and B₁ containing l-cystathionine were found to be responsible for specific antimicrobial activity of the complex against Sclerotinia and Botrytis species.     

Biosynthetic relationship among aflatoxins B1, B2, M1, and M2.

Aflatoxins are a family of toxic, acetate-derived decaketides that arise biosynthetically through polyhydroxyanthraquinone intermediates. Most studies have assumed that aflatoxin B1 is the biosynthetic precursor of the other aflatoxins. We used a strain of Aspergillus flavus which accumulates aflatoxin B2 to investigate the later stages of aflatoxin biosynthesis. This strain produced aflatoxins B2 and M2 but no detectable aflatoxin B1 when grown over 12 days in a low-salt, defined growth medium containing asparagine. Addition of dichlorvos to this growth medium inhibited aflatoxin production with concomitant accumulation of versiconal hemiacetal acetate. When mycelial pellets were grown for 24, 48, and 72 h in growth medium and then transferred to a replacement medium, only aflatoxin B2 and M2 were recovered after 96 h of incubation. Addition of sterigmatocystin to the replacement medium led to the recovery of higher levels of aflatoxins B2 and M2 than were detected in control cultures, as well as to the formation of aflatoxins B1 and M1 and O-methylsterigmatocystin. These results support the hypothesis that aflatoxins B1 and B2 can arise independently via a branched pathway.     

6-Ketoprostaglandin F1 alpha, prostaglandins E2, F2 alpha and thromboxane B2 production by endothelial cells, smooth muscle cells and fibroblasts cultured from piglet aorta

After [3H]arachidonic acid labeling, cyclooxygenase products were qualitatively analysed in the media of each cultured vascular cell type by reverse-phase high-performance liquid chromatography (rp-HPLC). The prostaglandin E2, prostaglandin F2 alpha, 6-ketoprostaglandin F1 alpha and thromboxane B2 detected in the rp-HPLC radioactive profile were then quantified by radioimmunoassay (RIA) in separate sets of experiments. In preconfluent endothelial cells prostaglandin F2 alpha and 6-ketoprostaglandin F1 alpha were detected in equal amounts (49%), whereas after confluence 6-ketoprostaglandin F1 alpha represented 57% of total secretion (P less than 0.05). Smooth muscle cells secreted mainly prostaglandin F2 alpha (48%) and fibroblasts prostaglandin E2 (44%). Using the bioassay method, antiaggregatory activity was detected only in endothelial cells, though a small percentage of immunoreactive 6-ketoprostaglandin F1 alpha was encountered in smooth muscle cells and fibroblasts (13 and 10%, respectively). Radioimmunological analysis after rp-HPLC separation of the medium of endothelial cells showed that the anti-6-ketoprostaglandin F1 alpha antibody recognized, among other substances, an unidentified compound. Its retention time was similar to that of prostaglandin F2 alpha. This unidentified compound was not detected in the media from smooth muscle cells and fibroblasts.     

Specificity of E2F1, E2F2, and E2F3 in mediating phenotypes induced by loss of Rb.

The Rb/E2F pathway plays a critical role in the control ofcellular proliferation. Here, we report that E2F1, E2F2, and E2F3 make major individual contributions toward the in vivo phenotypic consequences of Rb deficiency. In the developing lens of Rb(-/-) embryos, loss of E2F1, E2F2, or E2F3 reduces the unscheduled proliferation of fiber cells, with the loss of E2F3 having the most pronounced effect. In Rb-deficient retinas, all three E2Fs contribute equally to the ectopic proliferation of postmitotic neuronal cells. In contrast, E2F1 is unique in mediating apoptosis in both Rb(-/-) lenses and retinas. In the central nervous system, loss of E2F1 or E2F3 can almost completely eliminate the ectopic DNA replication and apoptosis observed in Rb(-/-) embryos, and loss of E2F2 partially reduces the unscheduled DNA replication and has no effect on apoptosis. These results provide clear evidence for functional specificity among E2Fs in the control of Rb-dependent proliferation and apoptosis in a tissue-specific manner.     

Cytology of F1 hybrids and chromosome number of F2 and BC1 progeny of the cross Bromus riparius x B. inermis

Summary Hybrids between B. inermis Leyss (2n=8x=56) and B. riparius Rehm. (2n=10x=70) were easily made. The F₁ hybrids had a fertility of 20%–50% under open pollination and backcrossing to B. inermis. Chromosome pairing in B. riparius was predominantly as bivalents (29.04–33.85 per cell for plant means). Bivalents also predominated in the F₁ hybrid (2n=9x=63) and there was a high level of pairing with no reduction in chiasma frequency. It was impossible to estimate the frequency of auto-versus allosyndetic pairing. Chromosome pairing in a hybrid between B. arvensis (2n=2x=14) and B. riparius confirmed that the B. riparius complement is capable of complete autosyndetic pairing. Chromosome numbers in the F₂ progeny ranged from 2n=56 to 72 but they were skewed towards 2n=63 to 70. Backcrosses ranged from 2n=56 to 63, as expected, with the distribution skewed towards 2n=56. Selection towards the 2n=56 level would be difficult in the F₂. Empirical observation suggested that cytoplasm had a major influence on morphology in the backcrosses. Additional studies are required to determine the best breeding scheme to introgress germ plasm between B. inermis and B. riparius.