SEARCH · Search PubMed

Results for “Microbial turnover”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources

PubMed2003

Novel functions of the phosphatidylinositol metabolic pathway discovered by a chemical genomics screen with wortmannin.

We report a novel connection between the phosphatidylinositol (PI) metabolic pathway and the DNA replication and damage checkpoint pathway discovered from an unbiased chemical genomics screen. Substrates and products of PI kinases are important signaling molecules that affect a wide range of biological processes. The full collection of yeast deletion strains was screened to identify genes that confer altered sensitivity to the natural product wortmannin, a PI kinase inhibitor. These experiments have allowed us to explore metabolomic and proteomic implications of PI synthesis and turnover. This study also uncovers other biological processes affected by wortmannin treatment, including proteasome-mediated degradation and chromatin remodeling. Bioinformatic analyses were used to reveal the relative distances among cellular processes affected by wortmannin and protein-protein interactions in the wortmannin-sensitive proteomic subnetwork. These results illustrate the great utility of using a whole-genome approach in annotating the biological effects of small molecules and have clear implications for pharmacogenomics. Furthermore, our discovery points to a route to overcoming genome instability, a result of defective DNA damage signaling/repair and a hallmark of cancer.

Androstadienes↗

PubMed2006

Using experimental manipulation to assess the roles of leaf litter in the functioning of forest ecosystems.

The widespread use of forest litter as animal bedding in central Europe for many centuries gave rise to the first litter manipulation studies, and their results demonstrated that litter and its decomposition are a vital part of ecosystem function. Litter plays two major roles in forest ecosystems: firstly, litterfall is an inherent part of nutrient and carbon cycling, and secondly, litter forms a protective layer on the soil surface that also regulates microclimatic conditions. By reviewing 152 years of litter manipulation experiments, I show that the effects of manipulating litter stem from changes in one, or both, of these two functions, and interactions between the variables influenced by the accumulation of litter can result in feedback mechanisms that may intensify treatment effects or mask responses, making the interpretation of results difficult.Long-term litter removal increased soil bulk density, overland flow, erosion, and temperature fluctuations and upset the soil water balance, causing lower soil water content during dry periods. Soil pH increased or decreased in response to manipulation treatments depending on forest type and initial soil pH, but it is unclear why there was no uniform response. Long-term litter harvesting severely depleted the forests of nutrients. Decreases in the concentrations of available P, Ca, Mg, and K in the soil occurred after only three to five years. The decline in soil N occurred over longer periods of time, and the relative loss was greater in soils with high initial nitrogen concentration. Tree growth declined with long-term litter removal, probably due to lower nutrient availability. Litter manipulation also added or removed large amounts of carbon thereby affecting microbial communities and altering soil respiration rates. Litter manipulation experiments have shown that litter cover acts as a physical barrier to the shoot emergence of small-seeded species; further, the microclimate maintained by the litter layer may be favourable to herbivores and pathogens and is important in determining later seedling survival and performance. Litter manipulation altered the competitive outcomes between tree seedlings and forbs, thereby influencing species composition and diversity; changes in the species composition of understorey vegetation following treatments occurred fairly rapidly. By decreasing substrate availability and altering the microclimate, litter removal changed fungal species composition and diversity and led to a decline in populations of soil fauna. However, litter addition did not provoke a corresponding increase in the abundance or diversity of fungi or soil fauna.Large-scale long-term studies are still needed in order to investigate the interactions between the many variables affected by litter, especially in tropical and boreal forests, which have received little attention. Litter manipulation treatments present an opportunity to assess the effects of increasing primary production in forest ecosystems; specific research aims include assessing the effects of changes in litter inputs on the carbon and nutrient cycles, decomposition processes, and the turnover of organic matter.

Biomass↗

PubMedDate not supplied

The effect of Saccharomyces cerevisiae and Aspergillus oryzae on the digestion of the cell wall fraction of a mixed diet in defaunated and refaunated sheep rumen.

The objective of this study was to determine the effect of two probiotics, Saccharomyces cerevisiae (SC) and Aspergillus oryzae (AO), without their culture medium, on the digestion of plant cell wall components in sheep that had been successively defaunated and refaunated. Six sheep fitted with large rumen cannulae were used to study 1) defaunated sheep with no probiotic, 2) defaunated sheep with SC or AO, 3) refaunated sheep with no probiotic, 4) refaunated sheep with SC or AO. The apparent digestibility of the plant cell walls was not altered (P > 0.05) by the probiotics in defaunated sheep but was increased (P < 0.05) with SC (+16%) in refaunated sheep. Simultaneously, SC stimulated the growth of the protozoal population in the rumen. As noted in most previous experiments, the positive effect of the presence of protozoa on plant cell wall digestion (P < 0.001) was confirmed here. The effect (P > 0.05) of SC or AO on in situ ADF digestion was either not significant or negative in defaunated rumens, whereas it became positive in refaunated rumen after a residence time of 12 h. The improvement of in situ ADF digestion due to the presence of protozoa was significant (P < 0.05 for NDF; P < 0.001 for ADF). However, we could not determine whether this was a direct effect of protozoa or an indirect effect operating via bacteria. The limits of the nylon bag technique for evaluating the microbial activity are discussed in relation to the ability of protozoa to enter and grow in the bags, and the pH regulation inside the bags. The pH values below 5.5 noted inside the bags can significantly alter the bacterial and protozoal populations and limit the validity of the technique. SC increased (P < 0.05) the specific activity of CMCase and xylanase of the solid-adherent bacteria (SAB) isolated from the rumen digesta of refaunated sheep. Stimulation of both the bacterial activity and protozoa numbers could explain the positive effect of SC on cell wall digestion in the rumen since the modelling of marker excretion in faeces showed that the ruminal mean retention time of hay measured from the model of Danhoa et al. was not modified (P > 0.05) by either refaunation or the presence of probiotics. AO increased (P < 0.05) the total retention time of the solid particles in the whole digestive tract and increased the ruminal liquid volume in the refaunated animals but it had no effect on the protozoa population or on the polysaccharidase activity of the SAB, which could explain the absence of effect of AO on the total digestibility of plant cell walls. Both probiotics decreased the liquid turnover in defaunated rumens (P < 0.05) but neither had any effect (P > 0.05) on this parameter after refaunation. The improvement of plant cell wall degradation in the whole digestive tract is probably due to a stimulation of digestion at the rumen level as indicated by the higher activity of the SAB in rumen digesta and the growth of protozoa.

Animal Feed↗

PubMed1984

The persistence of drug resistant Escherichia coli strains in the majority faecal flora of calves.

Two groups of calves, one of three and the other of two animals, were purchased in markets and reared initially on a commercial veal unit for 1 month and 4 months respectively. They were then moved to the Veterinary School, Langford, and kept for a further 6 and 4 months respectively. The animals were sampled weekly and a continual turnover in the strains forming the majority Escherichia coli faecal flora was demonstrated for all calves. Antibacterial-drug resistance, as measured by an Antibiotic Resistance Index (ARI), increased after arrival on the veal unit and persisted at high levels during the whole of their stay. After moving to Langford the ARI fell. Initially there was a reduction in the average number of resistance determinants per resistant strain and then, after a delay of up to 8 weeks, by an increase in the proportion of isolates that were fully sensitive. The source of the sensitive strains was not ascertained, although their appearance was not associated specifically with either weaning or turning out to pasture.

Animals↗

PubMed1981

Proliferative diseases.

A unifying concept that excessive proliferation of cells and turnover of cellular matrix contribute significantly to the pathogenesis of several diseases, including cancer, atherosclerosis, rheumatoid arthritis, psoriasis, idiopathic pulmonary fibrosis, scleroderma and cirrhosis of the liver, is presented. As corollaries to this concept, the following topics are considered: (1) the role of polypeptide hormones and hormone-like mediators in the initiation, promotion and maintenance of proliferative responses; (2) alterations in collagen metabolism and collagenase activity; (3) the role of proteinases; (4) the potential use of inhibitors of proteinases for prevention of disease; and (5) the potential use of inhibitors of proliferative polypeptide hormones for prevention of disease. As specific proteolytic and proliferative biochemical mechanisms which contribute to the pathogenesis of disease become identified, there is a unique opportunity to develop new pharmacologic methods of prevention.

Cell Division↗

PubMed1978

Outer membrane-dependent transport systems in Escherichia coli: turnover of TonB function.

Recent reports demonstrated that the energy-dependent step of vitamin B12 uptake into cells of Escherichia coli rapidly declines after cessation either of the expression of the tonB gene or of general protein synthesis. It is shown here that inhibition of protein synthesis results in the decline, with similar kinetics, of all tonB-dependent processes, including sensitivity to colicins B and Ia, irreversible adsorption of phage phi80, and siderophore-mediated iron uptake. The role of ongoing TonB-dependent reactions on this lability of TonB function was investigated. Ferrichrome and the enterochelin precursor, 2,3-dihydroxybenzoate, caused both a moderate depression of B12 uptake activity in growing cells (reversed upon removal of the siderophore) and an acceleration of the loss of activity following inhibition of protein synthesis by addition of spectinomycin. Strains lacking the tonB-dependent siderophore uptake systems did not show these responses. The results suggest the consumption of tonB product during its action.

Bacterial Proteins↗

PubMedDate not supplied

Nutrient and hydrology effects on soil respiration in a northern Everglades marsh.

Microbial respiration in peat and overlying plant litter, as influenced by water level and phosphorus enrichment, was evaluated for an Everglades (Florida, USA) marsh ecosystem by measuring CO2 and CH4 release from soil-water microcosms. Intact cores of peat, overlying plant litter, and surface water were collected at seven locations in cattail (Typha domingensis Pers.) and sawgrass (Cladium jamaicense Crantz) stands along a phosphorus (P) enrichment gradient in Water Conservation Area 2A (WCA-2A). Each soil-water microcosm was outfitted with a controlled air circulation system whereby outflow gas from the headspace could be analyzed for CO2 and CH4 to determine flux of C from the soil-water column to the atmosphere. Gaseous C flux was determined for flooded conditions (10-cm water depth) and for water levels of 0, 5, 10, and 15 cm below the peat surface. Overall, decreasing water level resulted in significantly increased C flux, although rates were significantly higher under flooded conditions than under nonflooded, saturated-soil conditions, presumably due to O2 availability associated with algal photosynthesis within the litter layer in the water column. Carbon flux decreased significantly for sites increasingly distant from the primary hydrologic and nutrient inflows to WCA-2A. The microcosm study demonstrated that the C turnover rate was significantly increased by accelerated nutrient loading to the marsh, and was further enhanced by decreasing water level under drained conditions. Our results also demonstrated that photosynthesis within the water column is a potentially important regulator of C mineralization rate in the litter layer of the marsh system.

Carbon↗

PubMed2001

Functional dynamics in the active site of the ribonuclease binase.

Binase, a member of a family of microbial guanyl-specific ribonucleases, catalyzes the endonucleotic cleavage of single-stranded RNA. It shares 82% amino acid identity with the well-studied protein barnase. We used NMR spectroscopy to study the millisecond dynamics of this small enzyme, using several methods including the measurement of residual dipolar couplings in solution. Our data show that the active site of binase is flanked by loops that are flexible at the 300-micros time scale. One of the catalytic residues, His-101, is located on such a flexible loop. In contrast, the other catalytic residue, Glu-72, is located on a beta-sheet, and is static. The residues Phe-55, part of the guanine base recognition site, and Tyr-102, stabilizing the base, are the most dynamic. Our findings suggest that binase possesses an active site that has a well-defined bottom, but which has sides that are flexible to facilitate substrate access/egress, and to deliver one of the catalytic residues. The motion in these loops does not change on complexation with the inhibitor d(CGAG) and compares well with the maximum k(cat) (1,500 s(-1)) of these ribonucleases. This observation indicates that the NMR-measured loop motions reflect the opening necessary for product release, which is apparently rate limiting for the overall turnover.

Endoribonucleases↗

PubMed1972

Control of fatty acid synthesis in bacteria.

When glycerol-requiring auxotrophs of Bacillus subtilis are deprived of glycerol, the synthesis of fatty acids continues at an apparent rate of 20 to 50% that of supplemented cultures. The newly synthesized fatty acids are not incorporated into phospholipid and accumulate as free fatty acids. These molecules undergo a much more rapid turnover than phospholipid fatty acids, and the rate of turnover is sufficient to indicate that the rate of fatty acid synthesis in glycerol-deprived cultures is similar to that in supplemented ones. The average chain length of the free fatty acids is greater than that of the phospholipid fatty acids. Cells deprived of required amino acids also show a diminution in the apparent rate of fatty acid synthesis; however, in this case, the fatty acids accumulate in phospholipid, and no increase of the free fatty acid fraction is observed. It is argued on the basis of these findings that the control of lipid synthesis does not operate at the level of transacylation but must act on one or more of the reactions of the fatty acid synthetase.

Acetates↗

PubMed2002

Methods for study of protein dynamics and protein-protein interaction in protein-ubiquitination by electron paramagnetic resonance spectroscopy.

Ubiquitination is a post-translation modification whereby the C-terminal end of ubiquitin (Ub) is covalently attached to the amino group of a lysine in a target protein. Additional ubiquitin groups are added using Ub-Ub linkages to form a polyubiquitin chain. A 26S protease complex specifically binds polyubiquitinated proteins and degrades them in an ATP-dependent manner. The target lysine in the substrate protein resides in a domain that is recognized by the ubiquitination machinery in a temporally and spatially controlled manner. The accessibility and the molecular dynamics of the target domain for each protein substrate is expected to be distinctive and this article is intended to facilitate investigations in this uncharted research area of ubiquitination mediated protein turnover by means of site-directed spin labeling. Examples illustrate the methodology of electron paramagnetic resonance data acquisition and interpretation in terms of secondary and tertiary structure resolution of proteins and protein complexes. Analysis of the spin labeled side chain mobility, its solvent accessibility, the polarity of the spin label micro-environment and distances between spin labels allow to model protein domains or protein-protein interaction sites and their conformational changes with a spatial resolution at the level of the backbone fold. The structural changes accompanying protein function or protein-protein interaction can be monitored in the millisecond time range. These features make site-directed spin labeling an attractive approach for the study of protein--ubiquitin interaction and protein ubiquitination.

Computer Simulation↗

PubMed1972

Regulation of the bacterial cell wall: analysis of a mutant of Bacillus subtilis defective in biosynthesis of teichoic acid.

Bacillus subtilis 168ts-200B is a temperature-sensitive mutant of B. subtilis 168 which grows as rods at 30 C but as irregular spheres at 45 C. Growth at the nonpermissive temperature resulted in a deficiency of teichoic acid in the cell wall. A decrease in teichoic acid synthesis coupled with the rapid turnover of this polymer led to a progressive loss until less than 20% of the level found in wild-type rods remained in spheres. Extracts of cells grown at 45 C contained amounts of the enzymes involved in the biosynthesis and glucosylation of teichoic acids that were equal to or greater than those found in normal rods. Cell walls of the spheres were deficient also in the endogenous autolytic enzyme (N-acyl muramyl-l-alanine amidase). Genetic analysis of the mutant by PBS1-mediated transduction and deoxyribonucleic acid-mediated transformation demonstrated that the lesion responsible for these effects (tag-1) is tightly linked to the genes which regulate the glucosylation of teichoic acid in the mid-portion of the chromosome of B. subtilis.

Alanine↗

PubMed2000

Diagnostic particle agglutination using ultrasound: a new technology to rejuvenate old microbiological methods.

Microbial antigen in clinical specimens can be detected rapidly by commercial test-card latex agglutination, but poor sensitivity is a potential difficulty. Antigen detection by immuno-agglutination of coated latex micro-particles can be enhanced in comparison with the conventional test-card method in both rate and sensitivity by the application of a non-cavitating ultrasonic standing wave. Antibody-coated micro-particles suspended in the acoustic field are subjected to physical forces that promote the formation of agglutinates by increasing particle-particle contact. This report reviews the application of ultrasound to immuno-agglutination testing with several commercial antibody-coated diagnostic micro-particles. This technique is more sensitive than commercial card-based agglutination tests by a factor of up to 500 for fungal cell-wall antigen, 64 for bacterial polysaccharide and 16 for viral antigen (in buffer). The detection sensitivity of meningococcal capsular polysaccharide in patient serum or CSF has been increased to a stage where serotyping by ultrasound-enhanced agglutination is comparable to that achievable with the PCR, but is available more rapidly. Serum antigen concentration as measured by ultrasonic agglutination has prognostic value. Increasing the sensitivity of antigen detection by increasing the acoustic forces that act on suspended particles is considered. Employing turbidimetry to measure agglutination as part of an integrated ultrasonic system would enable the turnover of large numbers of specimens. Ultrasound-enhanced latex agglutination offers a rapid, economical alternative to molecular diagnostic methods and may be useful in situations where microbiological and molecular methods are impracticable.

Agglutination Tests↗

PubMed1989

Interactions of FCE 22101 with class I beta-lactamases.

Hyperproduction of chromosomal Class I beta-lactamase causes resistance to newer cephalosporins in Enterobacter cloacae, Citrobacter freundii, Serratia spp. and indole-positive Proteeae. We examined the interactions of FCE 22101 with these enzymes, measuring (i) antibiotic lability to pure enzyme, (ii) inducing power and (iii) activity against beta-lactamase-inducible strains and their -depressed and -basal mutants. Turnover numbers of FCE 22101 were between 0.7 and 1.5 molecules hydrolysed/min/enzyme molecule, compared with ranges of 0.5-40 for cefotaxime (950 for the Proteus vulgaris cephalosporinase) and 4400-22,000 for cephaloridine. FCE 22101 induced enzyme synthesis strongly below the MIC and antagonized labile weak inducers such as cefotaxime and mezlocillin. Like imipenem, but unlike newer cephalosporins, FCE 22101 had equal activity against inducible strains and derepressed mutants, and did not significantly select derepressed mutants from inducible populations. beta-Lactamase basal mutants of E. cloacae and C. freundii were four- to eight-fold more sensitive than inducible and derepressed organisms whereas beta-lactamase-basal, -inducible and -derepressed Proteeae and Serratia spp. were equally sensitive. This difference reflected the larger amounts of enzyme produced by the E. cloacae and C. freundii strains, rather than kinetic differences in enzyme activity.

Anti-Bacterial Agents↗

PubMed1971

Regulation of extracellular protease production in Bacillus cereus T: characterization of mutants producing altered amounts of protease.

Twenty-nine mutants of Bacillus cereus T were selected on casein agar for their inability to produce large amounts of extracellular protease. They all formed spores, and 27 were also auxotrophs for purines or pyrimidines. Upon reversion to prototrophy, a large fraction regained the capacity to produce protease. Conversely, reversion to normal protease production resulted in loss of the purine or pyrimidine requirement in a large fraction of the revertants. One spontaneous low-protease-producing pyrimidine auxotroph studied in detail grew as well as the wild type and produced spores which were identical to those produced by the wild type on the basis of heat resistance, dipicolinic acid content, density, and appearance in the electron microscope. The rate of protein turnover in the mutant was the same as the wild type. The mutant did grow poorly, however, when casein was the principal carbon source. A mutant excreting 5 to 10 times as much protease as the wild type was isolated as a secondary mutation from the hypoproducer discussed above. Loss of the pyrimidine requirement in this case did not alter the regulation of protease production. Although the secondary mutant grew somewhat faster in most media than the wild type, the final cell yield was lower. The spores of this mutant appeared to have excess coat on the basis of both electron microscopic and chemical studies. There appear to be closely related but distinct catabolic controls for both extracellular protease and spore formation. These controls can be dissociated as for the hypoproducers but can also appear integrated as for the hyperprotease producer.

Agar↗

PubMed1993

Teicoplanin-resistant Staphylococcus aureus expresses a novel membrane protein and increases expression of penicillin-binding protein 2 complex.

In the recent clinical trials of teicoplanin therapy of endocarditis caused by Staphylococcus aureus, at least one instance of the emergence of teicoplanin-resistant strains during therapy has been reported (G.W. Kaatz, S. M. Seo, N. J. Dorman, and S. A. Lerner, J. Infect. Dis 162:103-108, 1990). We have confirmed, using conventional electrophoresis of EcoRI-digested chromosomal DNA and pulsed-field gel electrophoresis of SmaI-digested chromosomal DNA, that the resistant strain (12873) (MIC, 16 micrograms/ml) is genetically very similar to the susceptible parent (12871) (MIC, 4 micrograms/ml). Kaatz et al. were able to select spontaneous teicoplanin-resistant mutants (10(-9)), suggesting that a single gene might be involved. We have shown that the mutation is highly stable during growth in the absence of teicoplanin. Using Tn551, we have selected insertion mutants of 12873 that become teicoplanin susceptible. We have examined a number of aspects of cell wall physiology in strains 12871 and 12873 and the teicoplanin-susceptible Tn551 mutants of 12873. 12873 was more susceptible to lysostaphin lysis than 12871 and the susceptible Tn551 derivatives of 12873. Autolysis in phosphate buffer (pH 7.5) and cell wall turnover rates were similar in 12871 and 12873. An analysis of membrane proteins revealed the expression of a ca. 35-kDa protein and increased expression of both polypeptides of penicillin-binding protein (PBP) 2 (PBP2) in 12873 relative to 12871 and the Tn551 mutants of 12873. This increased expression was not related to PBP2', since both strains were susceptible to oxacillin in 2% NaCl (MIC, < or = 0.25 microgram/ml) and cellular DNA from neither strain hybridized with a specific mec gene probe. Two independent Tn551 inserts have been mapped to a ca. 117-kb SmaI fragment of the chromosome. These data suggest the possibility that the mutation resulting in resistance to teicoplanin involves the regulation of expression of both polypeptides of PBP2 and a 35-kDa membrane protein.

Autolysis↗

PubMed1997

Induction of neurite outgrowth in PC12 cells by gamma-lactam-related compounds via Ras-MAP kinase signaling pathway independent mechanism.

Rat pheochromocytoma cells, PC12 cells, undergo differentiation in response to nerve growth factor (NGF). Although the Ras-MAP kinase signaling pathway has been shown to play a central role in the response to NGF, the precise mechanism which induces differentiation remains unclarified. Recently, several gamma-lactam-related microbial products were identified to induce neurite outgrowth in neuroblastoma cells. Therefore, we synthesized a series of gamma-lactam-related compounds and tested for their ability to induce neurite outgrowth in PC12 cells. We found that two compounds, MT-19 and MT-20, induced neurite outgrowth at concentrations as low as 1 microg/ml. MT-19 and MT-20 have an n-hexadecyl group and an n-dodecyl group, respectively, at the position N-1 of the gamma-lactam ring, and the modification of this group leads to partial or complete loss of activity. In addition, the modification of the methyl and hydroxyl group at C-5 leads to complete loss of activity, indicating a strict structure-activity relationship. Interestingly, MT-19 and MT-20 induced neurite outgrowth of PC12 cells which lack normal Ras function. Furthermore, these compounds did not induce MAP kinase activation, suggesting that MT-19 and MT-20 do not require the Ras-MAP kinase signaling pathway which is shown to be necessary and sufficient for NGF-induced neurite outgrowth. Consistent with this, none of the early- or late-response genes tested, which include fos, zif268, Nur77, vgf, and transin, was induced. However, the protein level of three neurofilaments was increased after the incubation with these compounds. Since the level of other cytoskeleton proteins including actin and tubulin remained constant, MT-19 and MT-20 specifically affected neurofilament synthesis and/or turnover. Taken together, these findings indicate that MT-19 and MT-20 induce neurite outgrowth by activating the downstream target of MAP kinase or by a novel mechanism which is distinct from the NGF-activated pathway.

Actins↗

PubMed1978

[Hepatic fibrosis--mechanism, dynamics and clinical consequences (author's transl)].

Hepatic fibrosis may result from collapse after hepatocellular necrosis or from new formation of connective tissue. Fibroplasia, particularly within the lobular parenchyma, is a dynamic process. Newer cellular and biochemical investigations clarified its various steps. The process begins with stimulation of cells to connective tissue formation and can be divided into (1) intracellular synthesis, (2) extracellular maturation, and (3) collagen breakdown. The turnover of the connective tissue in the liver is conspicuously increased in chronic hepatitis of any type, as indicated by an elevation of several cellular and metabolic parameters. They are particularly raised in chronic hepatitis and in alcoholic liver injury. Further development of these parameters in the future should facilitate the analysis of the dynamics of fibroplasia. The strongest stimuli for hepatic fibroplasia are hepatocellular necrosis and inflammation, but ethyl alcohol and steatosis are also stimulating, though to a lesser degree. This explains the particular elevation of the fibroplastic parameters in alcoholic hepatitis. It points, however, also to the possibility that cirrhosis might develop without significant hepatocellular necrosis and inflammation. Perihepatocellular, periductular, and septal fibrosis are the functionally most important localizations leading to additional hepatic injury. The initiation of these types of fibrosis by liver injury points to a vicious circle. Specific anti-fibroplastic therapy is still in infancy.

Chronic Disease↗

PubMed1977

Activation of the alternative complement pathway due to resistance of zymosan-bound amplification convertase to endogenous regulatory mechanisms.

The surface of zymosan (Zy), by affording a protected microenvironment for C3b and the amplification convertase stabilized by properdin, P,C3b,Bb, shifts the alternative complement pathway from slow fluid phase turnover to the amplification phase of its expression. This mode of activation is in contradistinction to that of the classical pathway, which follows conversion of a proenzyme, Cl, to its active form, C1. Under conditions in which the control proteins, C3b inactivator (C3bINA) and beta1H, completely, inactivated C3b on the sheep erythrocyte intermediate, EAC4b,3b, the activity of C3b bound to Zy,ZyC3b, was diminished by only one-third. Further, when ZyC3b was converted to ZyC3b,Bb,P there was an additional point of deregulation in that the convertase was resistant to beta1H-mediated decay-dissociation while P,C3b,Bb on the sheep erythrocyte exhibited the usual susceptibility to beta1H. That Zy alone could indeed promote rapid C3 cleavage by the alternative pathway through assembly and protection of the amplification convertase on its surface was demonstrated with a mixture of alternative pathway proteins, C3,B,D,P, C3bINA, and beta1H, that had each been purified to homogeneity. Interaction of these proteins at one-tenth their relative serum concentrations with Zy permitted low-grade inactivation of C3 and B to advance to the level of amplification after a 15 min lag period. Because the reaction of the purified proteins proceeded spontaneously when either regulatory protein was deleted, the effect of Zy was attributed to deregulation rather than to conversion of one of the proteins to a specific initiating state. The alternative pathway, through the normal presence of D, interacts with a microbial surface, such as Zy, to amplify deposition of C3b by circumvention of endogenous regulatory mechanisms, thereby augmenting host defense.

Animals↗