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At least 163 records · Page 9Linked to original sources

Perceptual information for the timing of interceptive action.

Time-to-contact is an important quantity for controlling activities which involve the timing of interactions with objects and surfaces in motion relative to an observer. Two alternative means for obtaining perceptual information that might be used to obtain the time-to-contact required to correctly time an interaction have been contrasted: a method based on the perception of distance and velocity, and a method due to Lee involving a perceptual variable called tau. A monocular version of the first method is presented and shown to place a highly unrealistic and arbitrary limitation on the capabilities of the visual system. The second method is reviewed and its limitations discussed. Several means by which these limitations can be overcome are presented. Recently reported results from experiments which involved catching self-luminous balls in the dark are interpreted in terms of timing information available to the subject, and the notions of intermodal and multimodal timing information are introduced. Finally, the possibility that timing information is available to an observer which does not involve the variable tau is considered. It is concluded that many questions regarding the perception of time-to-contact remain unresolved and that much empirical research remains to be done.

Acceleration↗

Expression and distribution of ion transport mRNAs in human nasal mucosa and nasal polyps.

CONCLUSIONS: Our results indicate that the electrogenic kidney Na(+)/HCO(3)(-) cotransporter (kNBC), KCl cotransporter (KCC1 and -4) and Ca(2+)-activated Cl(-) channel (CaCC1, -2, -3) mRNAs are expressed in normal nasal mucosa and nasal polyp, suggesting that altered expression of all CaCC mRNAs in nasal polyp may cause impaired electrolyte and water transport across the epithelial cells. OBJECTIVE: Electrolyte transport by nasal epithelia has been suggested to be important for controlling the quantity and composition of the nasal fluid and may play an important role in the development of nasal polyps. Transepithelial transport of ions and water in various fluid-transporting epithelia is strictly dependent on the localization of specific membrane proteins in the polarized epithelial cells. In this study we investigated the expression and distribution of mRNA transcripts for kNBC, pancreatic NBC, KCC1, -2, -3, -4 and CaCC1, -2, -3 gene families in human nasal mucosa and nasal polyp. MATERIAL AND METHODS: The expression and localization of these gene families were investigated in inferior turbinate tissues and nasal polyp using reverse transcriptase polymerase chain reaction (RT-PCR), semiquantitative RT-PCR and in situ hybridization. RESULTS: mRNAs for kNBC, KCC1 and -4 and all the CaCC families (CaCC1, -2 and -3) are expressed in human turbinate mucosa and nasal polyp. The expression levels of kNBC and KCC1 and -4 mRNAs did not differ between nasal mucosa and nasal polyp. However, the expression levels of all the CaCC genes were significantly decreased in nasal polyp. In situ hybridization revealed that the expression of these genes was mainly localized in the epithelial layer and submucosal glands of inferior turbinate mucosa and in the epithelial layer of nasal polyp.

Adult↗

Bcl-2 inhibits the mitochondrial release of an apoptogenic protease.

Bcl-2 belongs to a family of apoptosis-regulatory proteins which incorporate into the outer mitochondrial as well as nuclear membranes. The mechanism by which the proto-oncogene product Bcl-2 inhibits apoptosis is thus far elusive. We and others have shown previously that the first biochemical alteration detectable in cells undergoing apoptosis, well before nuclear changes become manifest, is a collapse of the mitochondrial inner membrane potential (delta psi m), suggesting the involvement of mitochondrial products in the apoptotic cascade. Here we show that mitochondria contain a pre-formed approximately 50-kD protein which is released upon delta psi m disruption and which, in a cell-free in vitro system, causes isolated nuclei to undergo apoptotic changes such as chromatin condensation and internucleosomal DNA fragmentation. This apoptosis-inducing factor (AIF) is blocked by N-benzyloxycarbonyl-Val-Ala-Asp.fluoromethylketone (Z-VAD.fmk), an antagonist of interleukin-1 beta-converting enzyme (ICE)-like proteases that is also an efficient inhibitor of apoptosis in cells. We have tested the effect of Bcl-2 on the formation, release, and action of AIF. When preventing mitochondrial permeability transition (which accounts for the pre-apoptotic delta psi m disruption in cells), Bcl-2 hyperexpressed in the outer mitochondrial membrane also impedes the release of AIF from isolated mitochondria in vitro. In contrast, Bcl-2 does not affect the formation of AIF, which is contained in comparable quantities in control mitochondria and in mitochondria from Bcl-2-hyperexpressing cells. Furthermore, the presence of Bcl-2 in the nuclear membrane does not interfere with the action of AIF on the nucleus, nor does Bcl-2 hyperexpression protect cells against AIF. It thus appears that Bcl-2 prevents apoptosis by favoring the retention of an apoptogenic protease in mitochondria.

Amino Acid Chloromethyl Ketones↗

A "stealth" approach to inhibition of lymphocyte activation by oligonucleotide complementary to the putative G0/G1 switch regulatory gene G0S30/EGR1/NGFI-A.

The putative G0/G1 switch regulatory gene G0S30/EGR1/NFGI-A show increased expression shortly after adding concanavalin-A (ConA) to cultured T lymphocytes. However, it is reported that lymphocytes from mice in which the gene has been deleted proliferate normally in response to ConA. This suggests that G0S30 expression is not critical for the response. Paradoxically, others report that proliferation of ConA-stimulated rat lymphocytes is inhibited by an antisense oligonucleotide complementary to G0S30. Because the G0S30 sequence is highly conserved between species, we used a similar oligonucleotide (differing by 1 base) to show for humans that the response to ConA is also inhibited. However, no oligonucleotide-induced changes in the concentrations of G0S30 protein or mRNA are detectable. This suggests that the oligonucleotide is not acting by influencing the expression of G0S30, and may be targeting another gene. The phosphorothioated oligonucleotide was maximally inhibitory at a 50 nM concentration, which is near to the "physiological" concentration found with CpG-containing oligonucleotides to activate mouse B lymphocytes. In the present work, increasing the concentration above 50 nM, or adding further quantities of control oligonucleotides, decreased the inhibition. It is suggested that by using low oligonucleotide concentrations (the "stealth" approach), one may avoid "tripping" an endogenous defense system directed against exogenous oligonucleotides, yet still get sufficient uptake to inhibit lymphocyte activation.

Base Sequence↗

Investigation of the stability of yeast rad52 mutant proteins uncovers post-translational and transcriptional regulation of Rad52p.

We investigated the stability of the Saccharomyces cerevisiae Rad52 protein to learn how a cell controls its quantity and longevity. We measured the cellular levels of wild-type and mutant forms of Rad52p when expressed from the RAD52 promoter and the half-lives of the various forms of Rad52p when expressed from the GAL1 promoter. The wild-type protein has a half-life of 15 min. rad52 mutations variably affect the cellular levels of the protein products, and these levels correlate with the measured half-lives. While missense mutations in the N terminus of the protein drastically reduce the cellular levels of the mutant proteins, two mutations--one a deletion of amino acids 210-327 and the other a missense mutation of residue 235--increase the cellular level and half-life more than twofold. These results suggest that Rad52p is subject to post-translational regulation. Proteasomal mutations have no effect on Rad52p half-life but increase the amount of RAD52 message. In contrast to Rad52p, the half-life of Rad51p is >2 hr, and RAD51 expression is unaffected by proteasomal mutations. These differences between Rad52p and Rad51p suggest differential regulation of two proteins that interact in recombinational repair.

Cysteine Endopeptidases↗

Progesterone-induced atresia of the proestrous dominant follicle in the bovine ovary: changes in diameter, insulin-like growth factor system, aromatase activity, steroid hormones, and apoptotic index.

The objective was to determine whether there were decreases in insulin-like growth factors (IGF)-I and -II and increases in low-molecular-mass IGF-binding proteins (IGFBPs) in association with an inhibition of aromatase activity (AA) and follicular fluid estradiol (E2) production during progesterone (P4)-induced dominant follicle atresia in cattle. Twelve cycling cows received a norgestomet ear implant at proestrus for 9 days and were assigned to control (n = 3) or P4-treated (n = 9) groups. Injections of P4 (150 mg, i.m.) were given on Days 3 and 4; Days 3, 4, and 5; or Days 3, 4, 5, and 6 of the implant period. Controls received injections of corn oil on Days 3, 4, 5, and 6. Ultrasonography of the dominant follicle and blood sampling were done daily. Unilateral ovariectomy was done one day after the last injection. The experiment was repeated with the remaining ovary (6 follicles/treatment group). Granulosa cells were cultured with radiolabeled testosterone to measure AA. Steroid hormones, IGF-I, and IGF-II were measured in follicular fluid by RIA. The follicular fluid IGFBP profile was quantified by Western ligand blotting. P4-treated cows showed a drastic reduction in AA in the dominant follicles, and follicular fluid E2 was several times lower than in controls. Moreover, in P4-treated groups, concentrations of follicular fluid IGF-I and IGF-II were lower than in controls. The quantity of low-molecular-mass follicular fluid IGFBPs increased in P4-treated groups. Accumulation of low-molecular-mass IGFBPs with a reduction in IGFs may be a mechanism of dominant follicle atresia during the bovine estrous cycle.

Animals↗

Demonstration of local immunosuppression with methylprednisolone in the sponge matrix allograft model.

This study evaluated the effect of locally delivered methylprednisolone on the systemic and local immune response in the sponge matrix allograft model. Polyurethane sponges were coated with peritoneal exudate cells from DBA/2 (H-2d) or C57Bl/6 mice (H-2b) and placed subcutaneously in C57BL/6 recipients 24 hr later. Each mouse received both a syngeneic and an allogeneic sponge graft. Local immunosuppression was effected by placement on day 0 of cellulose/matrix pellets containing a preparation of increasing quantity of controlled release MP or by daily intrasponge injection of MP. Local immunosuppression was demonstrated by decreased cytotoxicity on day 12 in the allogeneic sponge receiving MP directly, as compared with the groups that received MP in the opposite syngeneic sponge or no MP. This effect was noted at a specific MP dose (0.5 mg/kg/day). Absolute numbers of precursor cytolytic cells and mature cytolytic cells (determined by limiting dilution analyses) infiltrating the allografts were also decreased in the sponges receiving MP directly, relative to the groups receiving MP in the opposite syngeneic sponge. Maintenance of systemic (in contrast to local) immunity was also demonstrated. Animals treated with local MP into a simultaneously placed syngeneic sponge or in whom no MP was delivered became sensitized to a synchronous DBA/2 sponge and rejected a subsequent DBA/2 skin graft in second-set fashion. Conversely, animals that received local MP into their synchronous DBA/2 sponge rejected a subsequent DBA/2 skin graft or a third-party graft with first-set kinetics. The presence of local MP at the initial graft site prevented the animals from becoming sensitized to the presented alloantigen but did not keep the animal from developing a rejection response to a third-party skin graft with first-set kinetics. It appears that delivery of MP locally to the site of antigen is an effective method to modulate alloreactivity. In addition, the sponge matrix allograft appears to be a useful model for studying local immunosuppression.

Animals↗

Frequency versus relaxation oscillations in a semiconductor laser with coherent filtered optical feedback.

We investigate the dynamics of a semiconductor laser subject to coherent delayed filtered optical feedback. A systematic bifurcation analysis reveals that this system supports two fundamentally different types of oscillations, namely relaxation oscillations and external roundtrip oscillations. Both occur stably in large domains under variation of the feedback conditions, where the feedback phase is identified as a key quantity for controlling this dynamical complexity. We identify two separate parameter regions of stable roundtrip oscillations, which occur throughout in the form of pure frequency oscillations.

Journal Article↗

Gamma-glutamyl transpeptidase in rat epididymis: effects of castration, hemicastration and efferent duct ligation.

Gamma-Glutamyl transpeptidase (gamma-GT) was studied histochemically and biochemically in the rat epididymis after castration with or without testosterone treatment, or after hemicastration and ligation of the efferent ducts. There was a strong reaction to gamma-GT in the apical part of the epithelium in the caput epididymis, while in the corpus and cauda the reaction was confined mainly to the luminal contents. Castration caused a marked decline in epithelial gamma-GT activity within 10 days. Subsequent testosterone treatment (1 mg/day for 10 days) restored gamma-GT activity in the apical surface and lumen. After hemicastration of adult rats, and after hemicastration or ligation of the efferent ducts in immature 28-day-old rats, a small but significant (P less than 0.001) decrease was observed in gamma-GT activity in the epididymal caput compared to controls. The quantities of six other enzymes (beta-N-acetylglucosaminidase, beta-galactosidase, angiotensin-converting enzyme, alanyl amino-peptidase, dipeptidyl peptidase IV, acid phosphatase) also displayed significant changes after castration and restoration of activities by testosterone treatment. However, their distribution in the caput and cauda epididymis was more even than that of gamma-GT, and the changes after castration were less drastic. It is concluded that gamma-GT is a highly sensitive androgen-dependent secretory marker in the caput epididymis and may have an important function in sperm maturation.

Animals↗

Narcotism: dimensions of the problem.

It is evident that the indirect indicators that are used to provide some estimate of heroin use trends are susceptible to distortion by variables having little to do with total heroin use. A panel of indicators, employed together, moving in the same direction, are seen as the best information available, and confidence can be placed in their implications. We have witnessed a rapid increase in the use of heroin in the decade that began in 1960. From 1970 to 1973 a decrease occurred followed by an increase in prevalence that lasted about two years. Since 1975 there appears to have been a levelling off or even a slight decrease in heroin use with a shift of higher use patterns to the West Coast. These changes are the result of many factors on both the demand and the supply sides of the equation. There is reason to believe that the curve could slope sharply upward again if substantial efforts are not made to control the quantity of available heroin, to prevent the recruitment of new users and to treat those now overinvolved with the drug. However, heroin prevalence rates will not recede to the pre-1960 level in the foreseeable future, and immediate goals include lowering them even more.

Adolescent↗

Basin-wide analysis of the dynamics of fecal contamination and fecal source identification in Tillamook Bay, Oregon.

The objectives of this study were to elucidate spatial and temporal dynamics in source-specific Bacteroidales 16S rRNA genetic marker data across a watershed; to compare these dynamics to fecal indicator counts, general measurements of water quality, and climatic forces; and to identify geographic areas of intense exposure to specific sources of contamination. Samples were collected during a 2-year period in the Tillamook basin in Oregon at 30 sites along five river tributaries and in Tillamook Bay. We performed Bacteroidales PCR assays with general, ruminant-source-specific, and human-source-specific primers to identify fecal sources. We determined the Escherichia coli most probable number, temperature, turbidity, and 5-day precipitation. Climate and water quality data collectively supported a rainfall runoff pattern for microbial source input that mirrored the annual precipitation cycle. Fecal sources were statistically linked more closely to ruminants than to humans; there was a 40% greater probability of detecting a ruminant source marker than a human source marker across the basin. On a sample site basis, the addition of fecal source tracking data provided new information linking elevated fecal indicator bacterial loads to specific point and nonpoint sources of fecal pollution in the basin. Inconsistencies in E. coli and host-specific marker trends suggested that the factors that control the quantity of fecal indicators in the water column are different than the factors that influence the presence of Bacteroidales markers at specific times of the year. This may be important if fecal indicator counts are used as a criterion for source loading potential in receiving waters.

Animals↗

Active Fe-containing superoxide dismutase and abundant sodF mRNA in Nostoc commune (Cyanobacteria) after years of desiccation.

Active Fe-superoxide dismutase (SodF) was the third most abundant soluble protein in cells of Nostoc commune CHEN/1986 after prolonged (13 years) storage in the desiccated state. Upon rehydration, Fe-containing superoxide disumutase (Fe-SOD) was released and the activity was distributed between rehydrating cells and the extracellular fluid. The 21-kDa Fe-SOD polypeptide was purified, the N terminus was sequenced, and the data were used to isolate sodF from the clonal isolate N. commune DRH1. sodF encodes an open reading frame of 200 codons and is expressed as a monocistronic transcript (of approximately 750 bases) from a region of the genome which includes genes involved in nucleic acid synthesis and repair, including dipyrimidine photolyase (phr) and cytidylate monophosphate kinase (panC). sodF mRNA was abundant and stable in cells after long-term desiccation. Upon rehydration of desiccated cells, there was a turnover of sodF mRNA within 15 min and then a rise in the mRNA pool to control levels (quantity of sodF mRNA in cells in late logarithmic phase of growth) over approximately 24 h. The extensive extracellular polysaccharide (glycan) of N. commune DRH1 generated superoxide radicals upon exposure to UV-A or -B irradiation, and these were scavenged by SOD. Despite demonstrated roles for the glycan in the desiccation tolerance of N. commune, it may in fact be a significant source of damaging free radicals in vivo. It is proposed that the high levels of SodF in N. commune, and release of the enzyme from dried cells upon rehydration, counter the effects of oxidative stress imposed by multiple cycles of desiccation and rehydration during UV-A or -B irradiation in situ.

Amino Acid Sequence↗

Beneficial effects of intravenous glyceryl trinitrate in a case of Prinzmetal angina.

A case is described of the successful use of intravenous glyceryl trinitrate in controlling ischaemia-induced high-grade ventricular ectopic activity occurring in a patient during a Prinzmetal angina attack. The intravenous form of glyceryl trinitrate is probably more effective than the sublingual form in controlling arrhythmias arising during acute ischaemic episodes because of prompt delivery of the drug to the coronary circulation where vasodilation occurs. In addition,the ability to control the quantity and rate of drug delivery with an intravenous infusion offers distinct advantages in cases of coronary spasm occurring during situations such as coronary arteriography where it can be administered with careful electrocardiographic and haemodynamic monitoring.

Angina Pectoris↗

Treatment of experimental Bordetella bronchiseptica infection in young pigs with potentiated sulphonamide in the drinking water.

Bordetella bronchiseptica was eliminated from the nasal cavity of experimentally infected piglets after about three weeks by trimethoprim and sulphadiazine (potentiated sulphonamide) in the drinking water in two experiments (at levels of 13.3 and 66.7 micrograms per ml, respectively). The rhinitis and turbinate damage associated with the infection was significantly less when the animals were examined at seven weeks of age but daily weight gain was not improved to a significant extent compared with controls. Smaller quantities of potentiated sulphonamide were less active but no amount induced resistance in the bordetellae during the one month period of treatment.

Administration, Oral↗

Cloning, expression, and tissue distribution of a human amiloride-sensitive Na+ channel.

Amiloride-sensitive Na+ channels control, in part, fluid and electrolyte transport across epithelia in many organs. In the lung, they control the quantity and composition of the respiratory tract fluid and play a key role in the transition from a fluid-filled lung at the time of birth. Their function may also be altered in a number of diseases. The recent identification of an epithelial Na+ channel from rat colon allowed us to use a probe from that sequence to clone an amiloride-sensitive Na+ channel from human kidney, alpha hENaC. The cDNA had an open reading frame of 2,007 nucleotides and encoded a protein predicted to contain 669 amino acids. The amino acid sequence of alpha hENaC was 83% identical to that of the rat. The gene was mapped to chromosome 12 by polymerase chain reaction (PCR) of somatic cell hybrids. Transcripts of alpha hENaC were detected in human kidney, lung, liver, and pancreas. No message was detected in first- and second-trimester human fetal lung, indicating that alpha hENaC expression is developmentally regulated. In vitro transcription and translation of alpha hENaC produced a 74-kDa protein and translation in the presence of microsomal membranes produced a glycosylated 87-kDa protein. Expression of alpha hENaC in Xenopus oocytes produced currents that were amiloride sensitive and Na+ selective, properties consistent with the function of epithelial Na+ channels in native tissues.

Adult↗

Construction of an sIgE:FLAG-mIgE:GFP reporter mouse strain.

Like all other immunoglobulins, IgE can be secreted into the blood or expressed as a membrane receptor on the surface of B lymphocytes. Secreted immunoglobulins trace the antigen and contribute to its destruction. Membrane immunoglobulins accompany the B cell along its differentiation pathway, regulating processes like the induction and maintenance of immunological memory and differentiation of plasma cells. The regulation of the expression of IgE is very complex. A lot of positive and negative regulators influence the synthesis of IgE. In previous publications, we were able to show that the membrane IgE (mIgE) antigen receptor itself controls the quantity and quality of serum IgE produced. However, the knowledge about the regulatory function of the antigen receptor on these processes is at best limited. In the present paper, we present the construction of a reporter mouse strain, which will help us to follow an mIgE-bearing B cell during the immune response more precisely.

Animals↗

Regulation of the IgE response at the molecular level: impact on the development of systemic anti IgE therapeutic strategies.

The classical allergic reaction starts within seconds or minutes after antigen contact and is induced by antibodies produced by a special subset of B lymphocytes. These antibodies belong to the IgE subclass and are responsible for Type I hyper-reactivity reactions. IgE plays a minor role in healthy individuals. In allergic individuals, however, IgE antibodies trigger allergic responses through allergen-mediated cross-linking on effector cells followed by mediator release. The mechanisms inducing a switch to IgE production are not fully understood with the consequence that allergies are mainly treated with antisymptomatic drugs. To develop basic therapies, many questions concerning the very complex regulation of IgE expression have to be understood. Positive and negative regulators influence the synthesis of IgE. Experiments in our laboratory could show that not only regulatory molecules, but also the membrane bound IgE itself controls the quantity and quality of the IgE produced. This fact becomes more and more interesting, because the signals generated by the B-cell receptor may be important targets for interference in allergic patients, in whom the titer and the affinity of the IgE antibodies for the allergen are directly related to disease activity.

Adenine↗

Studies on human platelet gangliosides.

Gangliosides, glycosphingolipids which contain sialic acid, were studied in human platelets. They represented 0.5% of the platelet lipids and accounted for 6% of the total neuraminic acid content of platelets. Three major ganglioside fractions were identified and characterized. Ganglioside I was hematoside (G(6)) and comprised 92% of the platelet gangliosides. It contained glucose, galactose, and sialic acid in molar ratios of 1:1:1 and no hexosamine. The major fatty acid was behenate (22:0). Ganglioside I was also identified in isolated platelet granules and membranes. Ganglioside II (5%) contained glucose, galactose, sialic acid, and hexosamines (molar ratios 1:2:1:1). The hexosamines were glucosamine (72%) and galactosamine (28%). It was therefore designated as ganglioside lacto-N-neotetraose. Ganglioside III (2%) contained disialosyllactosyl ceramide (G(3A)) as well as two other gangliosides which could not be precisely characterized. Gangliosides I, II, and III were susceptible to the action of Clostridium perfringens neuraminidase as evidenced by full recovery of sialic acid in its free form after incubation. Neutral platelet glycolipids were qualitatively examined by thin-layer chromatography. The major component was lactosyl ceramide. Interactions of gangliosides I and III and serotonin-(14)C were examined in an equilibrium dialysis system at 4 degrees C. The gangliosides bound serotonin-(14)C in relatively small quantities, whereas control lipids were negative. The binding was essentially unchanged by reverse dialysis, ultracentrifugation and subsequent thin-layer chromatography. The results are comparable to the previously observed nonmetabolic interactions between whole platelets and serotonin in the cold. It is suggested that the orientation and specific distribution of platelet membrane glycolipids may be important determinants of the unique surface properties of platelets.

Blood Platelets↗