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PubMed1991

[Studies on calcium oxalate crystal formation in urolithiasis. Multi-regressive analysis of urinary CaOx crystalline volumes and the effects of urinary various substances on CaOx crystal formation].

Because human urine contains various substances which can affect each other, it is quite difficult to clarify the mechanism of formation of calcium oxalate (CaOx) crystal in urine. The authors recently determined CaOx crystalline content and the concentrations of other substances in urine specimens from patients with urolithiasis and healthy volunteers, and subjected the data to multi-regressive analysis for the purpose of assessing the effect of these urinary substances on CaOx crystal formation. 1. In analysis of urine from patients with urolithiasis, the partial correlation coefficients of CaOx crystal formation with oxalic acid, sodium, calcium, uric acid magnesium were 0.67, 0.28, 0.18, and -0.10, respectively. The formula of regression was as follows: Amount of CaOx crystal (X 10(6) microns3/ml) = 3.59 X 10(-2) Ox (mM/L) + 4.72 X 10(-3) Ca (mM/L) + 4.52 X 10(-3) Na (mM/L) + 2.51 X 10(-4) UA (mM/L) -2.39 X 10(-2) Mg (mM/L) -1.65. The multiple correlation coefficient was 0.759. Thus, in patients with urolithiasis, urinary crystal formation was most dependent on the oxalic acid level, sodium, calcium, and uric acid were found to promote crystal formation, while magnesium to suppress it. 2. In analysis of urine from healthy volunteers, the partial correlation coefficients of CaOx crystal formation with oxalic acid and inorganic phosphorus were 0.51 and -0.24, respectively. The formula of regression was as follows: Amount of CaOx crystal (X 10(6) microns3/ml) = 1.91 X 10(-2) Ox (mM/L) -3.43 X 10(-4) P (mM/L) +0.29 The multiple correlation coefficient was 0.525.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

PubMed1986

The pyruvate branchpoint in the anaerobic energy metabolism of the jumping cockle Cardium tuberculatum L.: D-lactate formation during environmental anaerobiosis versus octopine formation during exercise.

The cockle Cardium tuberculatum responds with a typical escape movement (jumping by foot contractions) when touched by a starfish. In addition, this species can survive anoxic conditions for up to 20 h at 22 degrees C. The maximum activities of various enzymes involved in energy metabolism were determined in foot, adductor muscle and gills. Three enzymes with pyruvate reductase activity (lactate-, octopine-, alanopine/strombine dehydrogenase) can possibly serve as the terminal step of anaerobic glycolysis. On the whole the activities of enzymes involved in aerobic metabolism are low. In whole specimens of C. tuberculatum the metabolic response to anoxic incubation, exercise and exercise following anoxia were investigated. During 15 h of incubation in oxygen-free sea water no significant change in the energy charge is observed. The levels of arginine-phosphate fall to 50% of the value in resting animals with a concomitant increase in arginine concentration, but virtually no formation of octopine occurs. D-lactate and alanine are the main end products of anaerobic glycolysis and accumulate to a similar extent during anoxic incubation. While D-lactate levels increase linearly with time, L-alanine exhibits a 2-h delay before concentrations begin to rise. There is little formation of succinate and no formation of propionate and acetate. Despite the remarkably high activities of the enzymes alanopine and strombine dehydrogenase only negligible amounts of alanopine are found after anoxia and no production of strombine occurs. Exercise results in a depletion of the arginine-phosphate stores, liberation of arginine and formation of octopine. In whole animals as well as in foot muscle these changes are closely correlated to the number of jumps performed. No accumulation of D-lactate, alanine and succinate was detected. Exercise after an anoxic preincubation period of 6 h results in a further depletion of the already diminished arginine-phosphate stores and formation of octopine as the only end product. During anoxia the contribution of glycolysis to the required energy is enhanced from 44% (after 2 h) to 86% (after 15 h). During exercise glycolysis contributes 36% of the energy demand but only 16% during exercise after anaerobic preincubation. Thus the direction taken at the pyruvate branchpoint can be predicted on the basis of the glycolytic flux. Octopine formation only occurs when the glycolytic flux is enhanced (during exercise at least 40-fold). At low glycolytic flux (60% reduction during anoxia) pyruvate is channelled to form D-lactate and alanine.

Alanine↗

PubMed1989

The molecular basis of granuloma formation in schistosomiasis. III. In vivo effects of a T cell-derived suppressor effector factor and IL-2 on granuloma formation.

Granuloma formation in schistosomiasis is characterized by the formation of a large lesion in acutely infected animals which subsequently decreases in size as disease progresses into the chronic phase. These in vivo studies confirm and extend previous in vitro observations on the regulation of granulomatous hypersensitivity by a T cell-derived suppressor effector factor (TseF). TseF regulation of granuloma formation in vivo and DTH are shown to be both antigenically and genetically restricted. This suppression is accompanied by a suppression of the ability of cells derived from TseF recipients to function in an in vitro assay of granuloma formation. Antigenic recognition, defined by cellular proliferation in response to antigenic stimulation, is uneffected by TseF administration. Administration of IL-2 reduces TseF function in acutely infected mice and results in increased liver granuloma size. However, the ability of cells derived from these animals to form granulomas in vitro is uneffected. Cells obtained from chronically infected IL-2 recipients do not produce TseF in vitro and granuloma size is increased in these animals. Animals receiving both IL-2 and TseF continue to demonstrate decreased granuloma formation, indicating that IL-2 does not effect the ability of preformed TseF to function. These observations suggest that TseF modulates granuloma formation in vivo and may interact with IL-2 in a dynamic process which determines the intensity of the granulomatous response.

Adjuvants, Immunologic↗

PubMedDate not supplied

Cytochrome P-455-nm complex formation in the metabolism of phenylalkylamines. VI. Structure--activity relationships in metabolic intermediary complex formation with a series of alpha-substituted 2-phenylethylamines and corresponding N-hydroxylamines.

The formation of cytochrome P-450 metabolic intermediary (MI) complexes from a homologous series of alpha-substituted 2-phenylethylamines and corresponding N-hydroxylamines was investigated during NADPH-dependent metabolism in liver microsomes from phenobarbital-pretreated rats. The alpha-alkyl substituent consisted of branched and unbranched alkyl chains ranging from 0-4 carbons and the benzyl group. All the compounds but 2-phenylethylamine generated the complex and double-reciprocal plots of the highest observed rate of complex formation vs. substrate concentration gave linear relations over a defined substrate range. The Vmax(obs) values for complex formation by the amines increased markedly with increasing size of the alkyl group and a good correlation was obtained between log Vmax(obs) and the logarithm of the octanol/buffer partition coefficient of the substrates. With the N-hydroxy compounds, complex formation was a much less selective phenomenon and without exception the rates were quite high with Vmax(obs) values as much as 100 times greater than those of the amines. The disappearance of substrate amines was independent of structure and at an initial substrate concentration of 100 microM about a 50% decrease was noted during a 20-min period in all cases. The results substantiate the previous notion that N-oxidation is a prerequisite for MI-complex formation from primary amines. The results also suggest that C- and N-oxidation have different rate-limiting steps and the microsomal enzymes catalyzing the N-oxidation seem to be deeply submerged in the lipid matrix, as amines with a low distribution are inactive or poor substrates for generating the cytochrome P-450 ligand. Also, it is evident that the MI complex formation does not impair the overall metabolism of the amines.

Animals↗

PubMed1998

Radiation-induced radical formation in beta-glycerophosphate single crystals studied by electron paramagnetic resonance and electron nuclear double resonance spectroscopy: formation of an allylic-type radical.

Single crystals of disodium beta-glycerophosphate pentahemihydrate (betaGP), Na2x(HO)CH2CH(PO(4)2-)CH2(OH)x5 1/2H2O, were X-irradiated at 77 and 280 K. EPR, ENDOR and FSE techniques were used to study the formation of free radicals in these irradiated crystals to characterize possible reaction mechanisms leading to dephosphorylation. Irradiation at 77 K reveals the presence of four different radicals: two alkoxy radical conformations, AR1 and AR2, (HO)CH2CH(PO(4)2-)CH2O. and two carbon-centered hydroxyalkyl radicals, LTR1, (HO)CH2CH(PO(4)2-) C.HOH, and LTR2, with a tentative structure (HO)CH2C.H(PO(4)2-)CH2OH. AR1 and AR2 were determined to be formed on each of the two independent molecules A and B of the asymmetrical unit of betaGP, each on the 3-end of the molecule. Irradiation at 280 K reveals the presence of three hydroxyalkyl allyl radicals, R1, R2 and R3, with the common chemical structure (HO)C.H-H=CH(OH). Radicals R1 and R2 are determined to form on molecules B and A of the asymmetrical unit, respectively. The site of radical formation for R3 could not be ascertained absolutely from the available data, and there is also evidence that suggests the possibility that R3 has a hydroxyphospho-allyl radical structure. Possible reaction mechanisms for the formation of both the 77 K radicals and the 280 K radicals are suggested and discussed. The formation of an allyl-type radical in such a small-molecule single-crystal model system is an interesting and surprising result which may be relevant to the formation of the so-called 3alphaH radical species commonly observed in irradiated solid cytosine nucleosides and nucleotides. The result is also important because of the formation of the hydroxyalkyl allyl radical in solid beta-glycerophosphate is at variance with mechanisms and products shown to dominate for this and similar systems in solution radiolysis.

Crystallization↗

PubMed1984

Anaerobiosis, formate, nitrate, and pyrA are involved in the regulation of formate hydrogenlyase in Salmonella typhimurium.

Three groups of mutants defective in the fermentative production of gas were isolated from Salmonella typhimurium LT2 subjected to transposition mutagenesis with Mu d(Apr lac). One group consisted of strains which lacked hydrogenase. The mutation site for this group was located in the vicinity of the known hyd gene. A second group consisted of mutants which lacked the formate dehyrogenase associated with hydrogenase. The mutation site was located in four of them. It was not in the vicinity of the previously described fhlD gene but was instead located at 93 min on the Salmonella map. The third mutant group, which consisted of strains that produced gas in triple sugar iron agar but not in nutrient agar supplemented with glucose, appeared to be pyrA mutants. The insertion site was located in the vicinity of pyrA , and they required arginine and pyrimidines for growth. Expression of the lac operon in the hyd mutants was induced by anaerobiosis. It was only slightly increased by the addition of formate under anaerobic conditions and slightly decreased by the addition of nitrate. Nitrate had no effect in an hyd ::Mu d strain that also carried a chlC::Tn10 insertion. Full expression of the lac operon in the fhl mutants required both formate and anaerobic conditions. The presence of nitrate in addition to formate resulted in activities about half those obtained in its absence, even in the fhl ::Mu d chlC::Tn10 double mutant. In the absence of formate, nitrate reduced expression only in the fhl ::Mu d single mutants. Expression of the lac operon among the pyrA mutants was repressed by arginine and cytosine and also by anaerobiosis. An explanation for the involvement of pyrA in aerobic and anaerobic energy metabolism is proposed.

Aerobiosis↗

PubMed1981

T lymphocyte colony-forming capacity of patients with immunodeficiency diseases: relationship of colony formation to E rosette formation and lymphocyte proliferation.

The formation of T lymphocyte colonies was studied in 30 normal subjects and 12 patients with suspected abnormalities in immune function. The mean number of colonies per plate in normal subjects was 1.159 +/- 411 which represented a plating efficiency of 0.5-1.0%. When individual cells from colonies of these normal subjects were studied for membrane markers, greater than 90% were E rosette-positive and less than 1% were positive for surface immunoglobulins. Blood lymphocytes obtained from all 12 patients showed diminished colony-forming capacity when compared to normal subjects with a range of 0-311 colonies. Six patients had less than 50 colonies/plate. Colony formation was diminished in some patients who had normal E rosette formation and lymphocyte proliferation in liquid culture. Because of these discrepancies it appears that colony formation is not a direct reflection of E rosette formation and lymphocyte proliferation. Evaluation of T lymphocyte colony-forming capacity may prove useful as an additional in vitro assessment of lymphocyte function.

Cell Division↗

PubMed2004

Fiber connections of the hippocampal formation and septum and subdivisions of the hippocampal formation in the pigeon as revealed by tract tracing and kainic acid lesions.

The organization of the pigeon hippocampal formation was examined by tract tracing by using biotinylated dextran amine (BDA) and cholera toxin B subunit (CTB) and by injections of kainic acid to produce excitotoxic lesions. The hippocampal formation was divided into seven subdivisions based on Nissl staining and intrinsic and septal connections: dorsomedial (DM), dorsolateral (DL), triangular (Tr), V-shaped layer, magnocellular (Ma), parvocellular, and cell-poor regions. DL was composed of dorsal and ventral portions and sent associational fibers to DM, the V-shaped layer, and Tr. DL had strong reciprocal connections with the densocellular part of the hyperpallium (HD) and projected to the dorsolateral corticoid area. DM had reciprocal fiber connections with the V-shaped layer, Ma, and DL as well as with several subdivisions of the arcopallium. DL and DM, but not the V-shaped layer, projected fibers to the septum where those from DM exceeded in number those from DL. These projections further extended to the hypothalamus, particularly the lateral hypothalamic area. The lateral and medial septal nuclei projected back a very small number of ascending fibers to the hippocampal formation. Intraventricular injections of kainic acid induced neuronal loss widely in the hippocampal formation and subsequently produced gliosis in DM. These results indicate that DL receives its main afferents from HD and in turn sends inputs to an intrinsic circuit composed of hippocampal subdivisions DM, Ma, Tr, and the V-shaped layer; and also that DM is the main exit to the septum and hypothalamus. It is suggested that neurons in the V-shaped layer are intrinsic. Together, the results suggest that the V-shaped layer is comparable to the dentate gyrus of the mammalian hippocampal formation and that DM incorporates components comparable to both Ammon's horn and the subiculum.

Animals↗

PubMed1993

High-dose gestagens modulate bone resorption and formation and enhance estrogen-induced endosteal bone formation in the ovariectomized mouse.

To determine if gestagens of two separate classes have differing skeletal actions, we studied the effects of pharmacologic doses of norethisterone acetate (NETA), a 19-nortestosterone, and megestrol acetate (MA), a 17 alpha-hydroxyprogesterone, on bone formation and resorption in intact and in ovariectomized mice. In the same set of experiments, we also attempted to determine if these gestagens can alter the skeletal activity of 17 beta-estradiol (E2). Experimentally, the skeletons of 78 female BALB/c mice were prelabeled with [3H]tetracycline (3H-T). The animals were randomized to 13 groups of 6 mice each 3 days after the final 3H-T injection. Ovariectomies (OVX) were performed on 8 groups and sham operations (SO) on 5 groups. To study the skeletal effects of the gestagens, 4 groups each of the OVX and SO mice were treated with controlled-release pellet implants calculated to deliver 80 or 250 micrograms of NETA or MA per day. To study gestagen interactions with E2, 3 groups of OVX mice were treated with either 40 micrograms/day of E2 or 40 micrograms/day of E2 plus 250 micrograms/day of NETA or MA. One group of OVX and one group of SO animals received placebo pellets. Fluorochrome labels were administered 10 and 11 and 3 and 4 days before sacrifice to allow histomorphometric evaluation of bone formation. At the end of the 60 day protocol, tibiae and thoracic vertebrae were removed and processed for quantitating the levels of bone resorption based on the amounts of 3H-T retained in the bones. The femora were fixed and embedded for comparison of diaphyseal bone histomorphometry, and the humeri and lumbar vertebrae were prepared for bone density determinations. Reflecting an increase in bone resorption, 3H-T levels in tibiae and vertebrae were decreased in placebo-treated OVX animals compared to the placebo-treated SO group (p < 0.01). Treatment of both SO and OVX mice with NETA decreased bone resorption in a dose-dependent manner, but MA had no significant effects on vertebral bone resorption and increased bone resorption in the tibiae (p < 0.01). E2 treatment of OVX mice reduced bone resorption, but there were no significant interactions between the E2 and gestagen treatments on resorptive activity. Based on bone histomorphometry of in vivo fluorochrome labels, both gestagens increased periosteal bone formation rates but had no effect on endosteal bone formation (BFRe). In contrast, E2 treatment of the OVX mice stimulated bone formation at the endosteal surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

PubMed1995

Competition for factors and cellular resources as a principle of pattern formation in Hydra. II. Assistance of foot formation by heads and buds and a new model of pattern control.

In Hydra long-range interactions between head, bud, and foot formation take place in addition to short-range interactions which are recognized as induction phenomena, occurring when transplants are placed into an environment of disparate positional value. Here the long-range promotion of foot formation is analyzed. The data show: (1) While head regeneration and the onset of budding are mutually inhibitory, in particular in Hydra vulgaris and strain reg-16 of Hydra magnipapillata, fully developed heads and advanced buds cooperatively support foot formation in both the bud and the parent. Utilizing these interdependences H. vulgaris can be caused to form ectopic feet and to regenerate feet at both ends of excised segments. (2) The foot-promoting activity returns late in head regeneration, as late as the apparent long-range "head inhibition" determined in transplantation studies. (3) While periodic treatment with diacylglycerol (DAG) increases the capacities to form heads and buds, the potency to form feet is transiently reduced. (4) When treatment with DAG is finished the elevated capacities to form heads and buds subside, in reg-16 and H. vulgaris there followed a phase of ectopic foot formation. (5) The foot does not promote head regeneration. Based on the results of this and previous studies the following hypotheses are proposed: (1) Heads and buds compete for resources, such as precursor cells and soluble head-promoting factors that are distributed in the interstitial spaces. (2) The ability to make use of these resources is associated with positional value and decreases down the body column. The decreasing capability is attributed to a decreasing complement of receptors for the head-promoting factors. (3) Feet are made by body regions which are the losers in the competition for these factors. (4) Superiority in the ability to compete for the locally available factors enables transplants to develop head structures, and inferiority causes them to form a foot. (5) Depletion of the head-promoting factors in the whole body column is a significant component of the "head inhibition potential" and mediates the assistance of heads and buds in foot formation. (6) A surplus of resources causes supernumerary head structures and delays or prevents foot regeneration. These interpretations have reference to a new receptor-based model of pattern control and are contrasted with prevailing hypotheses.

Animals↗

PubMed1997

Analysis of cell movement and signalling during ring formation in an activated G alpha1 mutant of Dictyostelium discoideum that is defective in prestalk zone formation.

Mound formation in the cellular slime mould Dictyostelium results from the chemotactic aggregation of competent cells. Periodic cAMP signals propagate as multiarmed spiral waves and coordinate the movement of the cells. In the late aggregate stage the cells differentiate into prespore and several prestalk cell types. Prestalk cells sort out chemotactically to form the tip, which then controls all further development. The tip organises cell movement via a scroll wave that converts to planar waves in the prespore zone leading to rotational cell movement in the tip and periodic forward movement in the prespore zone. Expression of an activated G alpha1 protein under its own promoter leads to a severely altered morphogenesis from the mound stage onwards. Instead of forming a tipped mound, the cells form a ring-shaped structure without tip. Wave propagation pattern and dynamics during aggregation and mound formation in the mutant are indistinguishable from the parental strain AX3. However, at the time of tip formation the spiral waves that organise the late aggregate do not evolve in a scroll-organising centre in the tip but transform into a circularly closed (twisted) scroll ring wave. This leads to the formation of a doughnut-shaped aggregate. During further development, the doughnut increases in diameter and the twisted scroll wave converts into a train of planar waves, resulting in periodic rotational cell movement. Although biochemical consequences resulting from this mutation are still unclear, it must affect prestalk cell differentiation. The mutant produces the normal proportion of prespore cells but is unable to form functional prestalk cells, i.e., prestalk cells with an ability to sort out from the prespore cells and form a prestalk zone. Failure of sorting leads to an altered signal geometry, ring-shaped scroll waves, that then directs ring formation. This mutant demonstrates the importance of prestalk cell sorting for the stabilisation of the scroll wave that organises the tip.

Animals↗

PubMed1988

ATP formation onset lag and post-illumination phosphorylation initiated with single-turnover flashes. III. Characterization of the ATP formation onset lag and post-illumination phosphorylation for thylakoids exhibiting localized or bulk-phase delocalized energy coupling.

When 100 mM KCl replaced sucrose in a chloroplast thylakoid stock suspension buffer, the membranes were converted from a localized proton gradient to a delocalized proton gradient energy coupling mode. The KCl-suspended but not the sucrose-suspended thylakoids showed pyridine-dependent extensions of the ATP onset lag and pyridine effects on post-illumination phosphorylation. The ATP formation assays were performed in a medium of identical composition, using about a 200-fold dilution of the stock thylakoid suspension; hence the different responses were due to the pretreatment, and not the conditions present in the phosphorylation assay. Such permeable buffer effects on ATP formation provide a clear indicator of delocalized proton gradients as the driving force for phosphorylation. The pyridine-dependent increases in the onset lags (and effects on post-illumination phosphorylation) were not due to different ionic conductivities of the membranes (measured by the 515 nm electrochromic absorption change), H+/e- ratios, or electron transport capacities for the two thylakoid preparations. Thylakoid volumes and [14C]pyridine equilibration were similar with both preparations. The KCl-induced shift toward a bulk-phase delocalized energy coupling mode was reversed when the thylakoids were placed back in a low-salt medium. Proton uptake, at the ATP-formation energization threshold flash number, was much larger in the KCl-treated thylakoids and they also had a longer ATP formation onset lag, when no pyridine was present. These results are consistent with the salt treatment exposing additional endogenous buffering groups for interaction with the proton gradient. The concomitant appearance of the pyridine buffer effects implies that the additional endogenous buffering groups must be located on proteins directly exposed in the aqueous lumen phase. Kinetic analysis of the decay of the post-illumination phosphorylation in the two thylakoid preparations showed different apparent first-order rate constants, consistent with there being two different compartments contributing to the proton reservoirs that energize ATP formation. We suggest that the two compartments are a membrane-phase localized compartment operative in the sucrose-treated thylakoids and the bulk lumen phase into which protons readily equilibrate in the KCl-treated thylakoids.

Adenosine Triphosphate↗

PubMed2000

[Effect of periosteum on induced bone formation by autolyzed, antigen-extracted, allogeneic bone. Determination of the extent of bone formation using quantitative computerized tomography].

Autolyzed, antigen-extracted, allogenic (AAA) bone is an osteoinductive preparation of completely demineralized bone matrix. It has been clinically applied for years. In an experimental study in rabbits, we evaluated the influence of cortical bone and periosteum on the amount of bone formation following augmentation with AAA bone. Two implants of standardized size were placed on the femoral bone of rabbits. A cell-excluding PTFE membrane was wrapped circularly around the femur as well as the anterior implant shielding the implant from the surrounding periosteum. The posterior implant was exposed directly to the periosteum while being shielded from the cortical bone by the membrane. Thus, two compartments were created selectively, preventing contact between the periosteum or cortical bone and the implants. For each compartment the area and volume of the induced new bone were evaluated by computerized radiograph analysis and quantitative CT (pQCT) scans. Implantation of AAA bone led to new bone formation in both compartments. Contact of the periosteum and the implant led to an almost four-fold increase in bone volume. Although bone formation showed interindividual variations, the difference of both compartments was highly significant using the Student's t-test for paired samples (P < 0.0001). The data show that periosteum is the primary source of new bone formation in augmentations with osteoinductive materials as it is rich in inducible progenitor cells and is well vascularized. In osseous augmentations with AAA bone, the periosteum should be preserved in order to achieve a close contact of the osteoinductive implant. Shielding from the periosteum, e.g., by cell-excluding membranes, leads to significantly less bone formation following implantation of AAA bone and should therefore be avoided.

Animals↗

PubMed2004

Transcriptional activation of p62/A170/ZIP during the formation of the aggregates: possible mechanisms and the role in Lewy body formation in Parkinson's disease.

Formation of intracellular inclusion bodies due to defects in the protein degradation machinery is associated with the pathogenesis of neurodegenerative diseases. Sequestosomal protein p62/A170/ZIP, which is an oxidative stress-related protein and a ubiquitin-binding protein, is a component protein of Lewy bodies that are observed in patients with Parkinson's disease. The association of p62 with poly-ubiquitinated proteins may be an important step in the formation of intracellular protein aggregates like Lewy bodies. To study the role of p62 in the formation of protein aggregates in PC12 cells, we monitored the intracellular localizations of p62 and ubiquitinated proteins and the levels of both components during treatment with MG132, a proteasome inhibitor. In the early stage of aggregate formation, p62 did not always co-localize with ubiquitin. In contrast, these proteins were always co-localized in later stages. After the treatment of the cells with MG132, we found that the expression level of p62 increased due to the transcriptional activation of the gene and that higher molecular sizes of p62, corresponding to mono- and di-ubiquitinated formes, were also formed. Both the transcriptional inhibitor actinomycin D and an antisense oligonucleotide of p62 inhibited the MG132-mediated increase of p62, the sequestration of ubiquitinated proteins, and the enlargement of the aggregates. Furthermore, p62-positive aggregates were observed primarily in surviving cells. Together, these results suggest that p62 plays an important role in the protection of cells from the toxicity of misfolded proteins by enhancing aggregate formation especially in the later stages.

Animals↗

PubMed2004

Comparing willingness-to-pay: bidding game format versus open-ended and payment scale formats.

The willingness-to-pay technique is being used increasingly in the economic evaluation of new health care technologies. Clinical trials of two methods of screening for colorectal cancer are currently being conducted in the UK and willingness-to-pay for screening has already been estimated by means of a questionnaire survey, using open-ended (OE) and payment scale (PS) formats. This paper addresses the same medical issue, although it elicits willingness-to-pay values by means of a bidding game in an interview setting. Interviews were conducted with 106 subjects in Nottingham. The bidding game format produced considerably higher valuations than had either of the previous questionnaire formats, whilst the significant differences between agreed valuations obtained using different initial bids supported the existence of starting-point bias in the bidding game. As with the questionnaire study, the majority of interview subjects offered relative valuations of tests at variance with their expressed preferences over the same tests. Given the significant difference in valuations generated by different formats, it follows that the economic case for preferring any one technology over others will depend considerably upon whichever format happens to have been used to generate the valuations.

Adult↗

PubMed2003

Formation of fine drug particle by cogrinding with cyclodextrins. Part II. The influence of moisture condition during cogrinding process on fine particle formation.

The purpose of this study was to investigate the effect of moisture condition during cogrinding process on fine drug particle formation. Cogrinding of cyclodextrins (CDs) and pranlukast (PRK) hemihydrate was performed in various moisture conditions at a mixing molar ratio of 2:1 (CDs:PRK) and the formation of PRK submicron particle was investigated. The moisture content in the cogrinding process significantly affected the fine particle formation. More than 90% of pranlukast loaded transformed to submicron particles when coground with alpha-CD, beta-CD or gamma-CD containing the specific amount of water for each CD system. Fine particle formation of PRK was considered as a particular phenomenon to cyclodextrins, since the submicron particles could not be formed when D-mannitol, lactose or microcrystalline cellulose (MCC) was used as a cogrinding additive. Moreover, the appearance and disappearance of fine particle formation was found to be reversible depending on the existence of water during the grinding process.

Chromones↗

PubMed1995

Evidence for H2 and formate formation during syntrophic butyrate and propionate degradation.

Both H2 and formate were formed during butyrate oxidation by Syntrophospora bryantii with pentenoate as electron acceptor and during propionate oxidation by a mesophilic propionate oxidizing bacterium (MPOB) with fumarate as electron acceptor. H2 and formate levels were affected by the bicarbonate concentration. S bryantii and MPOB were also able to interconvert formate and H2+ HCO3-; the apparent K(M) values for formate were of 2.9 mM and 1.8 mM, respectively. The conversion of H2+ HCO3- to formate was detected only when the H2 partial pressure was above 80 kPa. This interconversion seems to be rather unimportant under conditions prevailing during syntrophic propionate and butyrate oxidation.

Journal Article↗

PubMed2000

Formate dehydrogenase in rice plant: growth stimulation effect of formate in rice plant.

NAD-dependent formate dehydrogenase (FDH, EC 1.2.1.2.) plays a key role in the final step of the catabolism of methanol in methylotrophs. In certain plant species, this enzyme is a mitochondrial and NAD-dependent enzyme. In this study, the complete cDNA sequence of the rice (Oryza sativa cv Hinohikari) FDH gene, which contains an open reading frame (ORF) of 1128 bp, was determined. The sequence corresponds to a protein of 376 amino acids and shows strong homology to the NAD-dependent FDHs from other plants. Our experimental results showed that the expression of the rice cDNA in Escherichia coli induced FDH activity, indicating that the cDNA encodes a functional peptide of FDH. The application of formate to the roots of rice seedlings leads to growth increment both in terms of the length of the aerial part and the fresh weight. The FDH activity and the accumulation of FDH transcripts were strongly enhanced in the root portions of the formate-fed plants. This enhancement indicates that the transcriptional regulation which responds to formate functions in the rice plant, and that formate can act as an effective inducer for FDH activity.

Journal Article↗