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PubMed2026

An XRE-type regulator in Streptococcus mutans plays an important role in brpA expression and oxidative stress tolerance response.

This study used a functional genomics approach to explore the role of a xenobiotic response element (XRE)-type regulator (SMU.405c) in Streptococcus mutans physiology, including the expression of biofilm regulatory protein BrpA. Results showed that deletional mutation of xre significantly reduced the ability of the deficient mutant to grow in the presence of methyl viologen, a commonly used oxidative stressor (P < 0.001). When challenged in a hydrogen peroxide killing assay, the survival rate of the ∆xre mutant was >2-log less than the parent strain after 60 min (P < 0.001). Luciferase reporter fusion assays showed that xre deficiency had no significant effect on luciferase expression when it was under the control of the intact brpA promoter, but the reporter activity increased by >6-fold (P < 0.001) when the reporter gene was fused to a brpA promoter derivative with deletion of a putative XRE-binding box. Electrophoretic mobility shift assay (EMSA) showed that recombinant XRE interacted with the brpA promoter, resulting in an electrophoretic shift of the promoter probes. In vitro transcription assay also showed that inclusion of XRE caused transcription to fall off, significantly reducing full-length brpA transcripts. RNA-seq analysis revealed that deficiency of XRE led to altered expression of >102 genes by >2-fold (P < 0.05), including 28 with increased expression, and 74 with decreased expression. Among the down-regulated were genes for DNA repair and oxidative stress tolerance response. These results suggest that XRE (SMU.405c) in S. mutans plays an important role in brpA expression and oxidative stress tolerance response.IMPORTANCEStreptococcus mutans, a keystone pathogen in human dental caries, primarily lives in the highly diverse microbiota on tooth surfaces, where the conditions are often harsh and fluctuate frequently. Locus SMU.405c was annotated to encode a xenobiotic response element (XRE)-like transcriptional regulator, but no information is available concerning the role of this protein in S. mutans pathophysiology. This study used a functional genomics approach along with molecular and transcriptomic analysis to characterize a deletional xre mutant, and the results showed that xre deficiency in S. mutans resulted in weakened oxidative stress tolerance response and alterations in transcription of >102 genes, including those known to play an important role in cell envelope biogenesis and stress tolerance response. Reporter fusion assay, electrophoretic mobility shift assay (EMSA), and in vitro transcription further demonstrated that the XRE-like regulator encoded by SMU.405c is a repressor of brpA expression and plays an important role in oxidative stress tolerance response.

Streptococcus mutans↗

PubMed2025

Proper 5'-3' cotranslational mRNA decay in yeast requires import of Xrn1 to the nucleus.

The budding yeast Xrn1 protein shuttles between the nucleus, where it stimulates transcription, and the cytoplasm, where it executes the major cytoplasmic mRNA decay. In the cytoplasm, apart from catalyzing 5'→3' decay onto non translated mRNAs, Xrn1 can follow the last translating ribosome to degrade the decapped mRNA template, a process known as "cotranslational mRNA decay". We have previously observed that the import of Xrn1 to the nucleus is required for efficient cytoplasmic mRNA decay. Here by using an Xrn1 mutant that cannot enter the nucleus, but is otherwise functional in ribonuclease activity, we show that nuclear import is necessary for proper global cotranslational decay of mRNAs along coding regions and also affects degradation in the of 5' region of a large group of mRNAs, which comprise about 20% of the transcriptome. Furthermore, a principal component analysis of the genomic datasets of this mutant and other Xrn1 mutants also shows that lack of a cytoplasmic 5'→3' exoribonuclease is the primary cause of the physiological defects seen in a xrn1Δ mutant, but also suggests that Xrn1 import into the nucleus is necessary for its full in vivo functions.

Exoribonucleases↗

PubMed1979

Early necrectomy in deep burns of aesthetically and functionally important areas.

Deep burns of aesthetically and functionally important body areas in children may in their later growth and development have a decisive role. Of the total number (2743) of hospitalized children at the Burns Department of the Pediatric Surgery in Zagreb in the last ten years, deep burns of some aesthetically and functionally important body areas were separated and the results of the application of the early necrectomy and immediate grafting method, as recommended by Janzekovic, are analysed. It is concluded that the results, due to the strict and minute application of the method (considered are individual technically important details and solutions) are good in aesthetic and even more so in the functional sense. Very fast recovery of the functions as well as the fact that up till now no surgical corrections for functional disorders were necessary in analyzed areas, along with already known advantages of the early surgical treatment, undoubtfully speak for its application.

Burns↗

PubMed1979

[Syncope. An important border-line between neurology and internal medicine (author's transl)].

It is important for the neurologist to know the variations of the Adams-Stokes's attack so that the important differential diagnosis between an epileptic reaction and an Adams-Stokes's attack due to cardiac rhythmic disorder can be made. The Adams-Stokes's syndrome is not only due to asystoles in the sense of cardiac arrest but also to ventricular fibrillation and especially to the very common syndrome of the pathological sinoauricular node. The great importance of digitalis overdose is pointed out as an eliciting factor for the kind of arrhythmia which runs a course similar to that of the Adams-Stokes's syndrome.

Adams-Stokes Syndrome↗

PubMed1977

The importance of HLA matching in primary cadaveric kidney transplantation in Gothenburg.

The importance of HLA matching was studied for 319 primary cadaveric kidney transplantations during the period 1969-1976. During 1969-1972 the HLA match was the basis for recipient selection and most cases belonged to match grade 0 or 1. Graft survival was significantly better for match grade 0. Within match grade 1 cases with one foreign HLA B antigen had lower graft survival than cases with one foreign HLA A antigen, indicating the importance of the HLA B series. During 1973-1976 the HLA match was hardly considered in recipient selection. HLA matching during this period seemed to be of less importance, except for match grade 0 and the totally mismatched cases. When matching was performed for the HLA B series, it was found that graft survival was significantly improved when no or only one foreign HLA B antigen was present. The prognosis for cases with foreign HLA B antigen was significantly better during the later period.

Cadaver↗

PubMed1978

Nutritional importance of colostrum in the piglet.

Suckling of colostrum by piglets is very important in order to improve the survival rate. Colostrum provides maternal antibodies, energy and protein. Rearing piglets suckling an artificial milk of a similar chemical composition to that of sow's milk failed when the animals were housed in conventional conditions although numerous research workers succeeded in rearing 90% of animals delivered and fed in sterile conditions. Studies on the chemical analysis of colostrum showed a high dry matter content (30-40% higher than that of milk) in particular a high protein level (twice that of milk). The high proportion of globulins, i.e. 38% during farrowing, drops to 12% of the protein 4 days later; conversely the casein content rather low at birth doubles over the same period. Colostrum proteins are not used to proved energetic nutrients; some of them are absorbed without hydrolysis and have a special physiological rôle. The transmission of maternal immunity by gamma globulins is well known; lactotransferrin plays an important rôle as a transporter and a bacteriostatic factor. Enzymatic proteins such as lyzozyme govern the metabolism of glycoproteins. Hydrolyzed albumins, casein and proteose-peptone fraction provide the essential amino acids for de novo protein synthesis. The fat content is relatively low during the first 24 hours and increases threefold in the 4 days after farrowing. It provides the majority of the energy required by the young animal. A high proportion of some fatty acids, mostly oleic and linoleic acids, are used preferentially as sources of energy. Other components, including enzymes of the mammary cells, were found, but their particular rôle has not been explained. Colostrum contains in addition numerous vitamins (vitamins A and E) and some particular trace elements (iodine and selenium), and their transfer from the maternal diet to the young is particularity efficient by colostrum suckling. The nutritional rôle of those nutrients is important and their levels could affect the survival rate of the piglets. Hypotheses concerning the digestion and absorption of nutrients and antibodies are summarized, and finally, recommendations are made for further research and for the minimum amount of colostrum required by each piglet for survival and efficient postnatal growth to be assessed.

Animals↗

PubMed1978

Nutrition and its importance in dental health.

Balanced and good nutrition is necessary for the growth, development, and maintenance of the dental and oral structures. Nutrition counseling is, therefore, of paramount importance. The physician who is aware of the factors that cause dental and oral disease will be in a position to intercept the progress of dental caries caused by an incorrect diet. This paper considers the significance of highly cariogenic foods, particularly sucrose, and the difficulties of removing it from the diet. A method of conducting a diet survey is presented. The importance of fluoridation is discussed, with elaboration of the advisable prescribing techniques for fluoride supplementation of the diet. Cooperation between physician and dentist is important in order to insure the prevention of dental disease.

Adolescent↗

PubMed1976

Aboriginal new world epidemiolgy and medical care, and the impact of Old World disease imports.

Various workers, including T. D. Stewart, claim that the aboriginal Americas were relatively disease-free because of the bering Strait cold-screen, eliminating many pathogens, and the paucity of zoonotic infections because of few domestic animals. Evidence of varying validity suggests that precontact Americns had their own strains of treponemic infections, bacillary and amoebic dysenteries, influenza and viral penumonia and other respiratory diseases, salmonellosis and perhaps other food poisoning, various arthritides, some endoparasites such as the ascarids, and several geographically circumscribed diseases such as the rickettsial verruca (Carrion's disease) and New World leishmaniasis and trypanosomiasis. Questionably aboriginal are tuberculosis and typhus. Accordingly, virtually all the "crowd-type" ecopathogenic diseases such as smallpox, yellow fever, typhoid, malaria, measles, pertussis, polio, etc., appear to have been absent from the New World, and were only brought in by White conquerors and their Black slaves. My hypothesis is that native American medical care systems--especially in the more culturally advanced areas--were sufficiently sophisticated to deal with native disease entities with reasonable competence. But native medical systems could not cope with the "crowd-type" disease imports that struck Indian and Eskimos as "virgin-field" populations. Reanalysis of native population losses through a genocidal combination of diease, war, slavery and attendant cultural disruption by Dobyns, Cook and others strongly suggest that traditiona estimates underplayed the death toll by a factor of the general order of ten. This would make for an immediately pre-contact Indian population of some 90-111 million instead of the tradition 8-11 million. Evidence is growing that Indians may have been no more susceptible to new pathogens that are other "virgin soil" populations, and thus their immune systems need not be considered less effective than those in other people. Present-day high mortality rates in Indians of both continents from infectious disease imports may be more socioeconomic than anything else.

Delivery of Health Care↗

PubMed1977

Biologically important thiol-disulfide reactions and the role of cyst(e)ine in proteins: an evolutionary perspective.

Selected aspects of the reactions of thiols and disulfides are reviewed in an evolutionary context with special emphasis on the implications of the transition from a reducing to an oxidizing atmosphere on the earth. It is argued that thiols were important in prebiotic chemistry and in primitive metabolism but that disulfides, owing to their general instability in a reducing environment, came to be of importance as structural links in proteins only after the transition to an oxidizing atmosphere. The occurrence of glutathione is reviewed and discussed in terms of the role of glutathione in maintaining a reducing intracellular environment. The occurrence of cysteine and cystine in intracellular and extracellular proteins of bacteria and of animals is examined in terms of the redox state of the environment in which the protein functions. Thiol-disulfide changes associated with the dormant state are described and the role of cellular water content in dormancy is discussed. The potential significance of reactions between thiols and products of oxidative metabolism is discussed with special emphasis upon thiol additions to carbonyl and alpha, beta-unsaturated carbonyl groups and their possible role in steroid-receptor interaction.

Bacteria↗

PubMed1977

Locomotor stimulation by L-dopa: relative importance of noradrenaline receptor activation.

The importance of brain noradrenaline synthesis and receptor activation for the hyperkinesia induced by carbidopa plus L-Dopa in reserpine-treated or normal mice was analyzed in four different models. After pretreatment with reserpine and the monoamine oxidase inhibitor nialamide, the hyperkinesia induced by L-Dopa (25 mg/kg i.p.) was partly mediated via stimulation of noradrenaline receptors since it was significantly antagonized by the noradrenaline receptor-blocking agent phenoxybenzamine. Treatment with reserpine plus L-Dopa (125 mg/kg i.p.) produced an increase in motor activity probably due to stimulation of dopamine receptors since it was not accompanied by an accumulation of noradrenaline and it was not inhibited by phenoxybenzamine. The hyperkinesia following treatment with reserpine and a higher dose of L-Dopa (250 mg/kg i.p.) was probably due to stimulation of both dopamine and noradrenaline receptors since the dopamine-beta-hydroxylase inhibitor FLA-63 partly reduced the effect of L-Dopa. Phenoxybenzamine potentiated the motor stimulation by L-Dopa (125 mg/kg i.p.) in mice not pretreated with reserpine, perhaps depending on a slight enhancement of the net accumulation of brain dopamine. Thus, noradrenaline receptor activation is of importance for the L-Dopa-induced hyperkinesia, at least after high doses or after monoamine oxidase inhibition.

Animals↗

PubMed1977

Importance of free living mustelid carnivores in circulation of adiaspiromycosis.

The study of adiaspiromycosis in 8 species of free living mustelid carnivores (266 specimens) revealed the average intensity of infection to be 41.4%. The highest incidence rate was found in the exoanthropic species Putorius eversmanni (73.1%) and Martes martes (72.2%) while the lowest was observed in the hemisynanthropic species Putorius putorius (30.6%). The stone marten (Martes foina)) is a new, still unknown reservoir host of C. parvum var. crescens, C. parvum for which Putorius eversmanni and mustela nivalis are new hosts, was also demonstrated in 3 cases. In the present paper, the role of mustelid carnivores in natural foci of adiaspiromycosis is discussed and evaluated. The importance of these predators in the circulation of C. parvum var. crescens is relatively wide. They make possible the liberation of adiaspores from the lungs of their prey - primarily small mammals - into the environment and participate in the spread of infection in both the horizontal and vertical directions. They play a part in the process of distributing of the organism to the vicinity of human dwellings, in the development of new elementary foci, and also act as important reservoir hosts of C. parvum var. crescens.

Animals↗

PubMed1978

Renal abscess in children. A rare but important radiological diagnosis.

As in adults, renal abscess in children mimicks a tumoral syndrome. Renal abscess, although infrequent, should however be kept in mind because it is important to make an early diagnosis. The reason is simply that the treatment fo the two conditions is so different. Furthermore, an early accurate diagnosis avoids unnecessary investigations, such as arteriography, as well as unnecessary surgery. Four cases are reported in which the diagnosis of abscess was obtained by correlating both clinical and radiological findings. In only one case was arteriography performed and this was after treatment and it was normal. For an early diagnosis intravenous urography is of paramount importance. It shows a tumoral radiological pattern; in the context of clinical signs of suppuration (high fever, high leucocyte count and variably a urinary tract infection). The radiological findings suggest the diagnosis of abscess. On treatment the rapid regression and disappearance of the various clinical, laboratory, and radiological findings confirms the diagnosis of renal abscess.

Abscess↗

PubMed1979

[Medical development cooperation in the Confederation. The international framework and the important place of public health in Swiss development cooperation].

The systematic organization of health services in the developing countries to benefit the majority of the population is seen as an important contribution toward the general economic and social development of these countries. This view is uncontested today, but was given less importance in the early years of Swiss development aid. The Swiss Development Cooperation's support of health services is now integrated into its overall program to satisfy the basic needs of the people of the developing countries.

Developing Countries↗

PubMed1979

[Cross reactions of eight yeasts and their importance in serological Candida diagnostic (author's transl)].

While the antigen structure of yeast cell walls is well known, the immunological cross reactivity of these is often difficult to interpret. The cross reactions of eight yeasts were tested in rabbit hyperimmune sera by the indirect immunofluorescence test. Among the eight species examined were the medically important yeasts C. albicans, C. pseudotropicalis, C. krusei, C. parapsilosis, C. tropicalis, T. glabrata, and C. guilliermondii and the apathogenic yeast S. cerevisiae. It has been shown, that there is no correlation between the number of common antigens and the degree of cross reactivity which give identical titers. Therefore it appears, that the quantitative contributions of the single antigens have an important rule, i.e., some antigens are immunogenic in one species while having only hapten characteristics in another. Further the results show that in infections with C. krusei, C. pseudotropicalis, and C. guilliermondii homologous antigens have to be used for the serological diagnosis. The testing of human sera with the yeast antigens by the same methods showed that the strikingly distributions of the Candida titer and the Saccharomyces titer were similar. A larger number of sera of healthy people and patients were compared in the hemagglutination test. These results showed that pathological C. albicans titers cannot be caused by S, cerevisiae antibodies.

Antibodies, Fungal↗

PubMed1975

Aberrant hormone activity by tumors of gynecologic importance.

Increasing numbers of endocrine active tumors are being reported. The production of hormonal substances not generally associated with the tissues involved may directly or indirectly concern the gynecologist. Identification of these occurrences may be important in the diagnosis of occult neoplasms or obscure tumor effects. In addition, observation of the level of aberrant hormone secretion may be important therapeutic and prognostic measure. Detection may result from the investigation of apparent inappropriate and endocrine syndromes or routine screening in cases of known tumors. Proof of the actual production of hormone by the tumors and complete identification of the material in question generally requires extensive biologic, chemical, physical, and immunologic investigation. The most likely mechanisms for aberrant hormone production by tumors are derepression of the genome or the occurrence of chance biosynthetic anomalies coincident with neoplastic nuclear alterations. Endocrine active substances of interest to the gynecologist produced under these circumstances include gonadotropin, lactogens, thyrotropins, and adrenocortico-tropin, as well as calcium-mobilizing and erythropoietic substances.

Adrenocorticotropic Hormone↗

PubMed1977

Are the dorsal noradrenergic bundle projections from the locus coeruleus important for neocortical or hippocampal activation?

Three different methods were used to examine the importance of the dorsal noradrenergic bundle projections from the locus coeruleus (LC) in activation of the neocortex and hippocampus in freely moving rats. (1) After cerebral norepinephrine (NE) was depleted by systemic neonatal injections of 6-hydroxydopamine (6-OHDA) both atropine-resistant and atropine-sensitive forms of hippocampal rhythmical slow activity (RSA; theta) and neocortical low voltage fast activity (LVFA) remained intact. Compared to controls the adult rats treated with 6-OHDA in infancy reared less in a 24 h time sample of behavior and ran less in running wheels. (2) Brain dopamine and NE were also depleted by systemic injections of alpha-methyl-p-tyrosine. Following this treatment rats were very inactive behaviorally. However, normal activation of the hippocampus and neocortex was still present. (3) In normal rats, electrical stimulation of the LC was relatively ineffective, compared to stimulation of nucleus reticularis pontis caudalis, in producing behavioral changes (especially locomotion) or either atropine-resistant or atropine-sensitive hippocampal RSA or neocortical LVFA. It is concluded that the locus coeruleus is not important for cerebral activation, and that mechanisms for cerebral activation are probably diffusely represented in the reticular core. The data also show that when attempting to assess the effect of experimental manipulations on brain activity it is essential to control for the possible effects of changes in behavior.

Animals↗

PubMed1978

Importance of apolipoproteins in lipid metabolism.

Lipids, which serve as a source of energy and are an important constituent of cell membrane structure, are readily stored in the body. By definition they are insoluble in water. Specific proteins called apolipoproteins interact with lipids to form soluble lipid-protein complexes called lipoproteins. It is in this form that the major lipids--cholesterol, triglyceride and phospholipid--circulate in plasma. Unesterified fatty acids, another major lipid group, are bound to albumin in the circulation. The plasma lipoproteins are complex macromolecules composed of lipids, apolipoproteins and carbohydrates. The relative proportions of these components differ markedly between lipoprotein classes. Hyperlipidemia is a term used for increased concentrations of plasma cholesterol and/or triglycerides. Any one plasma lipid is present in several types of lipoproteins. Thus, hyperlipidemia implies the presence of hyperlipoproteinemia. The latter has important therapeutic implications. Most of the recent attempts at classification have been directed at the lipoprotein level of plasma lipid organization. Decreased concentrations of lipids in plasma can be achieved by altering the rates of metabolism of lipoproteins. Decrease in lipoprotein synthesis, increased catabolism or impaired release from cells into the blood stream may all result in a decrease of plasma lipids. Drugs which affect one or more of these factors are used to treat hyperlipoproteinemia. In order to elucidate the mechanism of action of hypolipidemic drugs it is necessary to understand the lipoprotein defect at the molecular level. This requires a more detailed knowledge of lipoprotein metabolism than is presently available for most of the hyperlipoproteinemias. This paper will review some of the generally accepted properties of the plasma lipoproteins, describe some difficulties which hamper the understanding of lipoprotein metabolism, and identify possible mechanisms by which drugs may affect lipoprotein metabolism.

Apolipoproteins↗

PubMed1977

Importance of glycerol and fatty acid residues on the ionic properties of phosphatidylglycerols at the air-water interface.

Ionic properties of didodecanoylphosphatidylglycerol (C12PG), didodecanolyphosphatidyl-l'-propanol (C12PP), di-(12-methyl, 13-methyl)-pentadecanoylphosphatidylglycerols (C15PG) and dihexadecanoylphosphatidylglycerol (C16PG) have been studied at the air-water interface using titration experiments at constant ionic strength and film expansion experiments at constant pH, with Li+, Na+, K+ and Cs+ in the subphase. For each lipid, the apparent pK in the surface is strongly dependent on the subphase salt concentration and differs from expected intrinsic pK in the bulk. Discrimination between alkaline cations is observed. These results can be accounted for by strong surface potentials, which are satisfactorily calculated by using the Gouy and Chapman theory of the diffuse double layer. The comparison of C12PP and PG expansion data shows the importance of the glycerol residue of PG ionic properties, favouring penetration of cations in the films. Lipids in the liquid-crystalline state, such as C12-and C15PG, do not interact with alkaline cations as does C16PG in the gel phase. In particular, film condensations bring about a clear-cut discrimination between Na+ and K+. Results are discussed with regard to cation penetration and the structure of water at the interface. The importance on membrane functions of these strong surface potentials generated by PG monolayers is suggested.

Air↗