Comparison of natriuretic,uricosuric, and antihypertensive properties of tienilic acid,bendrofluazide, and spironolactone.

The antihypertensive properties of the new diuretic tienilic acid were investigated. Thirteen previously untreated hypertensive patients took part in a double-blind crossover study in which 30 days'' treatment with tienilic acid 250 mg, bendrofluazide 5 mg, and spironolactone 100 mg were compared. Bendrofluazide caused the greatest natriuresis on the first treatment day and the most rapid fall in blood pressure. The ultimate antihypertensive effect of all three drugs was similar. Tienilic acid caused a noticeable reduction in serum urate concentrations and a rise in urate clearance, in contrast to the other two agents, which caused slight urate retention. Tienilic acid and bendrofluazide caused falls and spironolactone a rise in plasma potassium concentrations. No untoward effects were seen from any of the drugs. It is concluded that tienilic acid is a moderately potent diuretic that lowers plasma urate concentrations. It may be the drug of first choice for hypertensive patients who already have gout or are likely to develop it when taking thiazide diuretics.     

Effect of pH on pulmonary vascular tone, reactivity, and arachidonate metabolism

We studied the effects of perfusate pH on pulmonary vascular tone, reactivity, and thromboxane and prostacyclin synthesis in isolated buffer-perfused rabbit lungs. Extracellular acidosis did not affect base-line vascular tone, but alkalosis had a biphasic effect. Increasing the perfusate pH from 7.40 to 7.65 caused vasodilation, whereas raising pH to 7.70-8.10 caused vasoconstriction. Removing calcium (Ca2+) from the perfusate completely prevented the vasoconstriction caused by alkalosis. Perfusate pH strikingly affected pulmonary vascular reactivity. Acidosis inhibited the vasoconstriction caused by thromboxane and potassium chloride (KCl) but did not affect the response to angiotensin II. Alkalosis, in contrast, augmented the vasoconstriction caused by thromboxane and angiotensin II but reduced the vasoconstriction caused by KCl. Changes in pH also altered thromboxane and prostacyclin synthesis after the infusion of exogenous arachidonic acid (AA) or the endogenous release of AA by the lipid peroxide tert-butyl hydroperoxide.     

A pheromonotropic peptide of Helicoverpa zea,with melanizing activity,interaction with PBAN,and distribution of immunoreactivity

The sequence of an 18-amino acid residue peptide was deduced from the gene encoding PBAN and other peptides with common C-termini in Helicoverpa zea. The peptide caused melanization in larvae and pheromone production in females of H. zea, and was designated pheromonotropic melanizing peptide (Hez-PMP). The peptide has a 83% sequence homology with a pheromonotropic peptide isolated from Pseudaletia separata. PMP caused melanization and mortality when injected into larvae just before molting. Whereas intense melanization was caused with a dose of 1,000 pmol, peak mortality occurred at 100 pmol, with 50% of larvae dying within 48 h after injection. Pheromonotropic activity of PMP was dose dependent. Co-injection of Hez-PMP and Hez-PBAN into a female resulted in suppression of the pheromonotropic effect of PBAN. Whole-mount immunocytochemical studies revealed PMP-like immunoreactivity in frontal ganglion, subesophageal, thoracic, and abdominal ganglia as well as the esophageal nerve.     

Neuropharmacology of rotifer feeding,oviposition, and anesthesia

Effect of acetylcholine and anticholinergic drugs on feeding, oviposition, and anesthesia in rotifers was investigated. Neurotransmitter as well as antagonist drugs inhibited feeding in Brachionus calyciflorus in a dose-dependent manner. Most antagonist drugs caused an oscillating tachyphylaxis (drug habituation): the drug effect wore off and returned several times within an hour. Acetylcholine inhibited oviposition in Philodina acuticornis, and this effect was antagonized by all groups of anticholinergic drugs. The strongest antagonism was caused by neuromuscular blockers, and thus the cause of oviposition inhibition may be a cloacal sphincter spasm. Acetylcholinesterase inhibitory insecticides also antagonize the acetylcholine effect. Acetylcholine potentiates the anesthetic activity of ionizing local anesthetics (procaine, lidocaine) as well as that of atropine and the beta-adrenergic blocker propranolol. Muscarinic antagonists (atropine, benactyzine) and propranolol caused foot paralysis in B. calyciflorus, which is also potentiated by acetycholine. Further details of these results are given by Nogrady and Keshmirian (1986a, b).     

Effects of retinoids on differentiation, lipid metabolism, epidermal growth factor, and low-density lipoprotein binding in squamous carcinoma cells

The relationship among keratinocyte differentiation capacity, lipid synthesis, low-density lipoprotein (LDL) metabolism, plasma membrane composition, and epidermal growth factor (EGF) binding has been studied in SCC-12F2 cells. The differentiation capacity of the cells, i.e., ionophore-induced cornified envelope formation, was inhibited by various retinoids and stimulated by hydrocortisone. Retinoids that caused a significant reduction of cornified envelope formation, i.e., retinoic acid and 13-cis-retinoic acid, caused only minor changes in lipid synthesis and plasma membrane composition. Arotinoid ethylsulfone, having a minor effect on cornified envelope formation, caused a drastic inhibition of cholesterol synthesis, resulting in changes in the plasma membrane composition. Hydrocortisone stimulated cornified envelope formation but had only minor effects on lipid synthesis and plasma membrane composition. Of all retinoids tested, only arotinoid ethylsulfone caused a drastic increase in EGF binding, while hydrocortisone had no effect. Retinoic acid, arotinoid ethylsulfone, and hydrocortisone had no effects on LDL binding and only minor effects on LDL degradation. These results clearly demonstrate that the plasma membrane composition is not related to keratinocyte differentiation capacity, but most likely does determine EGF binding. Furthermore, EGF binding does not determine keratinocyte differentiation capacity.     

Effects of copper,chlorine, and thermal addition on the species composition of marine phytoplankton

The introduction of low levels of copper, chlorine, and thermal elevation caused significant changes in the biomass and species composition of natural phytoplankton cultured under ambient nutrient concentrations and natural light. Chlorine addition caused a rapid decline and copper a gradual decline in biomass relative to control assemblages. Both chlorine and copper additions led to a reduction in species diversity. Thermal addition of 2°C caused a slight increase in biomass, but did not affect species diversity. Higher levels of thermal addition during the summer led to greatly decreased levels of biomass. In general, addition of stress led to a reduction in centric diatoms, especially Chaetoceros spp., and predominance of microflagellates. These changes were more pronounced in copper- and heat-treated tanks than in the chlorine-treated tanks, perhaps due to rapid degradation of the added chlorine or nonspecific inhibition.     

The origin recognition complex in silencing, cell cycle progression, and DNA replication.

This report describes the isolation of ORC5, the gene encoding the fifth largest subunit of the origin recognition complex, and the properties of mutants with a defective allele of ORC5. The orc5-1 mutation caused temperature-sensitive growth and, at the restrictive temperature, caused cell cycle arrest. At the permissive temperature, the orc5-1 mutation caused an elevated plasmid loss rate that could be suppressed by additional tandem origins of DNA replication. The sequence of ORC5 revealed a potential ATP binding site, making Orc5p a candidate for a subunit that mediates the ATP-dependent binding of ORC to origins. Genetic interactions among orc2-1 and orc5-1 and other cell cycle genes provided further evidence for a role for the origin recognition complex (ORC) in DNA replication. The silencing defect caused by orc5-1 strengthened previous connections between ORC and silencing, and combined with the phenotypes caused by orc2 mutations, suggested that the complex itself functions in both processes.     

Effects of vinblastine, oncodazole, procarbazine, chlorambucil, and bleomycin in vivo on colchicine binding activity of tubulin.

Five chemotherapeutic agents which inhibit mitosis caused an $\text{in vivo}$ effect on the colchicine bound to the isolated tubulin from mouse lymphoma L5178Y cells. These effects were examined over a time course of 4, 12, 24, 48, and 72 hours after a single administration of each drug. Vinblastine, oncodazole, and bleomycin decreased the amount of colchicine bound per mg protein; procarbazine and chloroambucil increased the amount bound. All of the drugs except procarbazine required more than 4 hours to cause an effect on colchicine binding and in the case of bleomycin and oncodazole some recovery occurred after 48 hours. The mitotic index was affected by 4 hours by all drugs: procarbazine, chlorambucil and bleomycin caused a decrease; vinblastine and oncodazole, an increase.     

Cloning, characterization, and inactivation of the gene pbpC, encoding penicillin-binding protein 3 of Staphylococcus aureus

The gene pbpC from Staphylococcus aureus was sequenced: it encodes a 691-amino-acid protein with all of the conserved motifs of a class B high-molecular-weight penicillin-binding protein (PBP), including the transpeptidase conserved motifs SXXK, SXN, and KTG. Insertional inactivation of pbpC and introduction of the intact gene in a laboratory mutant missing PBP 3 showed that the pbpC gene encodes the staphylococcal PBP 3. Inactivation of pbpC caused no detectable change in the muropeptide composition of cell wall peptidoglycan and had only minimum, if any, effect on growth rates, but caused a small but significant decrease in rates of autolysis. Cells of abnormal size and shape and disoriented septa were produced when bacteria with inactivated pbpC were grown in the presence of a sub-MIC of methicillin.     

The murine homolog of SALL4, a causative gene in Okihiro syndrome, is essential for embryonic stem cell proliferation, and cooperates with Sall1 in anorectal, heart, brain and kidney development

Mutations in SALL4, the human homolog of the Drosophila homeotic gene spalt (sal), cause the autosomal dominant disorder known as Okihiro syndrome. In this study, we show that a targeted null mutation in the mouse Sall4 gene leads to lethality during peri-implantation. Growth of the inner cell mass from the knockout blastocysts was reduced, and Sall4-null embryonic stem (ES) cells proliferated poorly with no aberrant differentiation. Furthermore, we demonstrated that anorectal and heart anomalies in Okihiro syndrome are caused by Sall4 haploinsufficiency and that Sall4/Sall1 heterozygotes exhibited an increased incidence of anorectal and heart anomalies, exencephaly and kidney agenesis. Sall4 and Sall1 formed heterodimers, and a truncated Sall1 caused mislocalization of Sall4 in the heterochromatin; thus, some symptoms of Townes-Brocks syndrome caused by SALL1 truncations could result from SALL4 inhibition.     

A novel dodecadepsipeptide, cereulide, is an emetic toxin of Bacillus cereus

Abstract A vacuole-formation substance, cereulide of Bacillus cereus , is an emetic toxin in animals. Both oral administration and intraperitoneal injection of cereulide caused dose-dependent emesis in Suncus murinus , a new animal model of emesis. Vagotomy or a 5-HT₃ receptor antagonist completely abolished this emetic effect. Therefore, cereulide causes emesis through the 5-HT₃ receptor and stimulation of the vagus afferent. We also found that our purified cereulide caused swelling of mitochondria of HEp-2 cells.     

The antioxidant,U74389, ameliorates the depression of vascular reactivity caused by lipopolysaccharide

There is growing evidence that an oxidant stress contributes to the deleterious effects of bacterial lipopolysaccharide (LPS). The present study evaluated the ability of the antioxidant, U74389, to prevent the depression of vascular reactivity caused by LPS. Aortic rings taken from rats given LPS showed a depression of maximum force in response to phenylephrine that was reversed by an inhibitor of nitric oxide synthase. Pretreatment of animals with U74389 attenuated this depression of vascular reactivity. U74389 did not limit the increase in serum tumor necrosis factor levels caused by LPS. These results show that U74389 can ameliorate the depression of vascular reactivity caused by LPS possibly by interfering with the induction of nitric oxide synthase.     

Mechanism of the serotonin effect on motility of the duodenum,ileum, and jejunum in awake rabbits

I. v. administration of serotonin to alert rabbits produced a phasic change of contractile activity of duodenum, ileum, and jejunum including excitatory and inhibitory components. It is shown that stimulation of the small bowel motility is caused by serotonin activation of non-cholinergic excitatory mechanism with participation of effector cholinergic neurones. The initial suppression of the motility is caused by participation of nonadrenergic noncholinergic inhibitory mechanism, and the secondary inhibition of contractile activity of a small bowel with serotonin has an adrenergic nature.     

Phase responses in the circannual rhythm of the varied carpet beetle, Anthrenus verbasci, under naturally changing day length

In the varied carpet beetle, Anthrenus verbasci, we examined the effects on the circannual pupation rhythm of a short-day or long-day pulse under naturally changing day length at a constant 20 degrees C. A short-day pulse for 4 weeks caused a prominent phase delay or advance under constant long days, but had little or no effect on the phase under naturally changing day length between 4 August and 24 November. A long-day pulse for 4 weeks given under naturally changing day length caused a phase shift in the first pupation group, as under constant short days. A long-day pulse given on 4 August, 1 September, or 29 September caused a phase delay, and a pulse given on 27 October or 24 November caused a phase advance. Pupation was least synchronous just before the transition from delaying to advancing. However, the magnitude of phase delays was much smaller under natural day length than under short days. In the second pupation group, larvae pupated at the same time as in the control experiment without a long-day pulse, and this result can be attributed to entrainment to the geophysical year by long days in spring and summer.     

Osteology,myology and feeding mechanism of Astronotus ocellatus (Pisces,Perciformes)

Summary Astronotus ocellatus captures its prey by creating a negative pressure in the buccal cavity which is caused by its quick expansion. Once the prey has been accommodated, the buccal cavity undergoes a compression which may propel the prey towards the pharyngeal jaws for mastication. The motion picture recordings indicate retracted premaxillae at the beginning of food intake followed by a maximum attainment of mouth gape and then mastication. During the maximum opening of the mouth the premaxillae are protruded and dentaries are at maximum depression. These events are followed by activities such as buccopharyngeal cavity expansion, bulging on the ventral surface of the head, and prominent curvature on the ventral surface anterior to the urohyal, caused by the upward movement of the glossohyal. Based on the cinematographic results, it may be inferred that the maximum mouth gape is caused by the sternohyoid-hyoid-interopercular-mandible coupling, and not by the opercular apparatus-mandible coupling, as the latter acts after the full descent of the lower jaw. Impression of the expanded buccopharyngeal cavity has been made by a paraffin mold technique, which confirms the displacement of the buccopharyngeal elements during expansion of the cavity.     

Comparative effects of progesterone, norgestrel, norethisterone and tamoxifen on the abnormal uterus of the anovulatory rat.

Progesterone therapy results in partial reversibility of histological abnormalities of the rat uterus exposed to constant oestrogen stimulation and is associated with a decrease in nuclear oestrogen receptor content, which may underlie the tissue response to hormone treatment [White, Moore, Elder & Lim (1982) Biochem. J. 202, 535-41]. The synthetic progestins norgestrel and norethisterone used in this study were as effective as progesterone in decreasing the content of nuclear oestrogen receptor. However, only norgestrel had an ameliorative effect on epithelial hyperplasia and metaplasia. The non-steroidal anti-oestrogen tamoxifen caused a significant decrease in both nuclear and cytosol oestrogen receptor content without any change in luminal epithelial hyperplasia and metaplasia. Each progestin caused an increase, whereas tamoxifen caused a decrease, in the proportion of nuclear oestrogen receptors that were unoccupied. Each compound caused a decrease in the content of cytosol progesterone receptor. The effectiveness of compounds used as oestrogen antagonists is discussed with reference to their mode of action.     

Retinoic acid, midkine, and defects of secondary neurulation

BACKGROUND: Retinoic acid (RA) is necessary for normal differentiation of the tail bud into the secondary neural tube. Excess RA, however, is teratogenic and causes neural tube defects (NTDs). The way in which RA modulates secondary neurulation is unclear but probably involves RA-regulated downstream genes such midkine (MK), which encodes a growth factor implicated in tail bud mesenchymal-neuroepithelial conversion. Our objective was to determine whether RA-deficiency would produce similar defects and if MK is involved. METHODS: Citral, a drug that blocks endogenous RA formation, as well as a neutralizing antibody, were used to block RA activity in chick embryos. Immunohistochemistry and in situ hybridization were used to localize RA and MK in the tail bud. Competitive RT-PCR was used to examine the effects of excess RA and RA deficiency due to citral on the expression of MK mRNA. RESULTS: Citral-induced NTDs displayed a morphological resemblance to those caused by excess RA. However, citral treatment did not significantly increase embryonic mortality, and RA rescue of citral-treated embryos proved unsuccessful. MK mRNA was detected in the differentiating tail bud by in situ hybridization. Competitive RT-PCR showed that excess RA decreased MK expression by 60%. Doses of citral that caused a comparable incidence of defects, however, caused only a 25% decrease. CONCLUSIONS: The results show that excess RA and RA deficiency both cause defects of secondary neurulation. While excess RA decreased MK expression, RA deficiency had minimal effects. However, whether or not MK is an intermediary in the developmental phenomena regulated physiologically or pathologically by RA remains to be elucidated.     

Effect of spermine on proliferation of hyphae ofGlomus fistulosum, an arbuscular mycorrhizal fungus, in maize roots

Effects of two oligoamines, putrescine and spermine, on proliferation of intraradical hyphae in surface disinfected root segments were studied under axenic conditions in vitro. No significant effects of putrescine were observed. Spermine significantly stimulated hyphal growth at a concentration of about 1.5 mumol/L. High concentration (> 150 mumol/L) caused a strong inhibition of hyphal growth and of the percentage of root segments bearing proliferating hyphae. DL-alpha-difluoromethylornithine, a metabolic inhibitor of polyamine synthesis, caused a significant inhibition of proliferation of the hyphae only in the presence of 2 mumol/L spermine.     

Fixation, Counting, and Manipulation of Heterotrophic Nanoflagellates

Quantitative effects of several fixatives on heterotrophic nanoflagellates (HNAN) and phototrophic nanoflagellates (PNAN) were investigated by hemacytometer and epifluorescence counting techniques. Counts of Monas sp. cultures before and after fixation with unbuffered 0.3% glutaraldehyde and 5% formaldehyde showed no loss of cells during fixation, and cell concentrations remained constant for several weeks after fixation. Buffering of fixatives with borax caused severe losses, up to 100% within 2 h. Field samples from Lake Vechten showed no decline of HNAN and total nanoflagellate concentrations for at least 1 week after fixation with 5% formaldehyde and with 1% glutaraldehyde. With 1% glutaraldehyde, the chlorophyll autofluorescence of PNAN was much brighter than with 5% formaldehyde, although it was lost after a few days and thus limited the storage time of samples. However, when primulin-stained slides were prepared soon after fixation and stored at −30°C, the loss of autofluorescence was prevented and PNAN and HNAN concentrations were stable for at least 16 weeks. Effects of filtration and centrifugation on HNAN were also studied. Filtration vacuum could not exceed 3 kPa since 10 kPa already caused losses of 15 to 20%. Similar losses were caused by centrifugation, even at low speed (500 × g).     

The effects of cytokines, platelet activating factor, and arachidonate metabolites on C3B receptor (CR1, CD35) expression and phagocytosis by neutrophils

The cytokines tumor necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and interleukin 1 (IL 1) all caused an upregulation of C3b receptors (CR1) on neutrophils that ranged from around 76% (G-CSF and IL 1) to 93% (TNF alpha and GM-CSF) of the upregulation obtained by pretreatment of the neutrophils with the chemotactic peptide FMLP. However, only TNF alpha and G-CSF caused a significant increase in phagocytosis of opsonized microspheres. Platelet derived growth factor, interleukin 2, and transforming growth factor beta had no effect on either of these parameters. The mediators platelet activating factor (PAF) and leukotriene B4 (LTB4) both caused a large upregulation of CR1 (93% and 80%, respectively, of the FMLP-mediated value); however, only PAF caused a significant enhancement of phagocytosis by the neutrophils. Prostaglandin E2 and thromboxane B2 had no effect on these parameters. Considerable individual variation was observed among some of the untreated and mediator-treated neutrophil preparations regarding CR1 expression and phagocytosis. The upregulation of CR1 and associated increase in phagocytic capacity of neutrophils caused by certain cytokines and other mediators may be important in host defense. Also the lack of enhancement of phagocytosis accompanying an upregulation of CR1 is unusual and may have important implications regarding the cellular mechanisms of phagocytosis by neutrophils.