Biochemical mechanism of combined effect of ethambutol and sparfloxacin against Mycobacterium smegmatis

M. smegmatis cells grown in the presence of combination of ethambutol (EMB) and sparfloxacin (SPX) had decreased level of total cellular lipids as compared to control as well as cells grown in the presence of sub-inhibitory concentration (MIC50) of individual drugs. Amongst various phospholipids analyzed, maximum decrease was observed in the content of phosphatidylinositolmannosides (PIMs) of the cells grown in combination of EMB and SPX. In contrast, the subcellular distribution of phospholipids revealed a significant increase in PIMs content of both cell wall and cell membrane of the cells grown in the presence of combination of drugs as compared to control as well as individual drugs. Mycolic acids of M. smegmatis cells were found to be main targets as combination of drugs resulted in significant decrease in total cellular as well as cell wall mycolic acids as compared to control and individual drugs. Changed lipid composition of M. smegmatis cells grown in the presence of MIC50 of EMB, SPX and combination resulted in significant surface changes as was evident from decreased limiting fluorescence (Fmax) intensity of 1-anilinonaphthalene-8-sulfonate (ANS). Thus, the results of this study suggested that ethambutol and sparfloxacin in combination exerted their antimycobacterial effect principally due to their action on phosphatidylinositolmannosides (PIMs) and mycolic acids, which form the permeability barrier of mycobacteria.     

阿米巴巨大病毒及其潜在致病性研究进展

近年来,通过阿米巴共培养等方法发现了一批新的病毒,统称为巨大病毒（giant virus）。它们分布广泛,不仅有很大的病毒颗粒,基因组也非常庞大,还编码许多与蛋白质合成相关的基因,突破了人们对病毒的一般认识,引发了对病毒起源和本质的讨论。巨大病毒被认为有潜在致病性。本文综述了在人体中针对两类最早发现的巨大病毒--拟菌病毒（Mimivirus）和马赛病毒（Marseillevirus）开展的血清学、分子生物学、宏基因组检测、病毒分离及其对哺乳动物感染和致病性研究的进展     

Sites of gene activity and of inactive genes in polytene chromosomes of diptera

DNA has been found between bands, in puffs, and in RNA-rich lamellae of bands as dispersed DNA double helices coiled to form secondary helices with a diameter and period of about 400Å. In the bands and heterochromatic regions the secondary helix is further coiled or folded into compact masses. RNA-containing granules are present in interbands and RNA-rich lamellae as well as in puffs. The dispersed DNA of puffs, interbands and the RNA-rich lamellae of bands may all represent the part of the genome that is active in the salivary gland nucleus, while the compact DNA of bands as well as heterochromatic parts may comprise inactive genes.     

Structure-activity relationships of estrogens: effects of esterification of the 11 beta-hydroxyl group

Fourteen esters (formate, acetate, propionate, butyrate, hexanoate, heptanoate, and benzoate) located at C-11 of 11 beta-hydroxyesterone and 11 beta-hydroxyestradiol-17 beta were synthesized and evaluated for uterotropic and gonadotropin release inhibition in rats, as well as their ability to displace (3H) estradiol-17 beta from the rat uterine cytosolic estrogen receptor. The most potent uterotropic agent was 11 beta-formoxyestrone which was 1,625 or 2,500 times as active as 11 beta-hydroxyesterone in the uterotropic or gonadotropin release inhibition assay, respectively. 11 beta-Formoxyestrone was 7.5 times as uterotropic as estradiol-17 beta and equal to estradiol-17 beta in inhibiting gonadotropin release. However, the most potent inhibitor of gonadotropin release was 11 beta-acetoxy-estradiol-17 beta which had 133% of the activity of estradiol-17 beta, although it had only 38% of the activity of estradiol-17 beta in the uterotropic assay. Esters larger than the acetoxy group showed sharply decreased activities in either assay. Despite the high estrogenic potency of the 11-formates or 11-acetates, they were rather weak (6% to 35% as active as estradiol-17 beta) in displacing (3H) estradiol-17 beta from the rat uterine cytosolic estrogen receptor.     

The value of parameters of iron metabolism in the differential diagnosis of anemias]

As a result of investigations into the diagnostic validity of selected haematologic-morphological and clinical-chemical test factors of iron metabolism in the diagnosis of hypochromic anaemia, the examined test faktora are differently evaluated as individual parameters and in their combination. 1. Haematocrit (PCV) is equal to the determination of haemoglobin concentration as a search parameter. 2. The number of reticulocytes, copper and zinc as well as caeruloplasmin have a separating effect as individual parameters on the examined classes of iron deficiency and tumour and infect anaemia. 3. Iron has no value as a individual parameter. It is only in combination with TEBK and the haematologic test factors that is has a diagnostic value. 4. In contrast, ferritin as an individual parameter is of primary importance and should be used extensively in the laboratory diagnosis of hypochromic anaemia. 5. TEBK and transferrin may be supposed to be equal in their diagnostic value. 6. When used in combination, haemoglobin, MCV, TEBK, Transferrin, and ferritin have effective separating function. They permit hypochromic anaemia to be widely assigned to one or another kind of the examined classes.     

Governing Dementia: A Historical Investigation of the Power of States and Professionals in the Conceptualization of Dementia in China

This study intends to understand how Chinese states and healthcare professionals interact with each other in adopting biomedical concepts within the context of globalization of mental health. The conceptualization of dementia as a stigmatized mental disorder in China serves as a salient case to examine interactions between states and professionals as well as the interrelationships between different healthcare professionals in producing knowledge. By engaging the biopolitical approach, this project explores the historically-contingent conceptualizations of dementia, namely dementia as a vague and stigmatized condition in imperial China, dementia as biosocial deviance in Republican China, dementia as a product of capitalism during Mao-era China, and dementia as a stigmatized mental illness in contemporary China. These dynamics indicate that Chinese professionals have been largely influenced by state ideologies in assimilating biomedical concepts. Through the historical analysis of state-professional interactions in conceptualizing dementia, this study provides an avenue to understand how biomedical concepts transfer within the global context can be read as a site of power struggle between ethnomedicine and biomedicine, between various competing forms of healthcare professionals, and between indigenous sovereignty and governmentality. Moreover, the study of conceptualizing dementia in China sheds light on the larger sociopolitical processes of governmentality in China.     

Studies of the site and mode of biosynthesis of tobacco trichome exudate components

Detached glandular trichome head preparations and epidermal strips with and without trichome heads were used to identify glandular trichome heads as the site of sucrose ester biosynthesis in tobacco. Carbon dioxide in solution as well as sucrose, glucose, and acetate were shown to serve as precursors to both sucrose esters and duvatrienediol diterpenes in detached trichome heads or epidermal strips, and gaseous CO2 was also efficiently utilized by epidermal strips. Thus, glandular heads can biosynthesize these principal exudate components from a molecule as simple as CO2. While formation of duvatriendiols from all precursors tested and conversion of sucrose and glucose to sucrose esters was light dependent, utilization of acetate to label the 6-O-acetyl group of the glucose moiety of sucrose esters occurred equally well in light and dark. The data suggest that CO2 and/or monosaccharides produced in trichome head cells and perhaps that supplied by other epidermal cells can act as carbon sources for sucrose ester and duvatrienediol biosynthesis which occurs in the glandular trichome head.     

A set of modular binary vectors for transformation of cereals

Genetic transformation of crop plants offers the possibility of testing hypotheses about the function of individual genes as well as the exploitation of transgenes for targeted trait improvement. However, in most cereals, this option has long been compromised by tedious and low-efficiency transformation protocols, as well as by the lack of versatile vector systems. After having adopted and further improved the protocols for Agrobacterium-mediated stable transformation of barley (Hordeum vulgare) and wheat (Triticum aestivum), we now present a versatile set of binary vectors for transgene overexpression, as well as for gene silencing by double-stranded RNA interference. The vector set is offered with a series of functionally validated promoters and allows for rapid integration of the desired genes or gene fragments by GATEWAY-based recombination. Additional in-built flexibility lies in the choice of plant selectable markers, cassette orientation, and simple integration of further promoters to drive specific expression of genes of interest. Functionality of the cereal vector set has been demonstrated by transient as well as stable transformation experiments for transgene overexpression, as well as for targeted gene silencing in barley.     

Biotechnological uses of cyanobacteria

Cyanobacteria (blue-green algae) are 0₂-evolving photosynthesizing prokaryotes that have an extensive history of use as a human food source and as a fertilizer in rice fields. They have also been recognized as an excellent source of vitamins and proteins and as such are found in health food stores in North America and elsewhere. Cyanobacteria have a great deal of potential as a source of fine chemicals, as a biofertilizer and as a source of renewable fuel. This potential is being realized as data from research in the areas of the physiology and chemistry of these organisms are gathered and as the knowledge of cyanobacterial genetics and genetic engineering increases. We review, here, the present (and possible future) uses of cyanobacteria and assess the state of the art with respect to the genetic manipulation of cyanobacteria.     

Limitations of pH-potentiometric titration for the determination of the degree of deacetylation of chitosan

The degree of deacetylation (DDA) of chitosan determines the biopolymer's physico-chemical properties and technological applications. pH-Potentiometric titration seems to offer a simple and convenient means of determining DDA. However, to obtain accurate pH-potentiometric DDA values, several factors have to be taken into consideration. We found that the moisture content of the air-dry chitosan samples can be as high as 15%, and a reasonable fraction of this humidity cannot be removed by ordinary drying. Corrections have to be made for the ash content, as in some samples it can be as high as 1% by weight. The method of equivalence point determination was also found to cause systematic variations in the results and in some samples extra acid as high as 1 mol% of the free amino content was also identified. To compensate for the latter effect, the second equivalence point of the titration has to be determined separately and the analytical concentration of the acid be corrected for it. All the corrections listed here are necessary to obtain DDA values that are in reasonable agreement with those obtained from (1)H NMR and IR spectroscopic measurements. The need for these corrections severely limits the usefulness of pH-metry for determining accurate DDA values and thus potentiometry is hardly able to compete with other standard spectroscopic procedures, that is, (1)H NMR spectroscopy.     

Mechanisms of beneficial effects of probucol in adriamycin cardiomyopathy

Probucol, a lipid-lowering drug, has been shown to offer protection against adriamycin-induced cardiomyopathy. In order to define the mechanism of this protection, we examined changes in antioxidants and lipid peroxidation in hearts as well as lipids in hearts and plasma from rats treated with either adriamycin or adriamycin and probucol with appropriate controls. Any potential free radical quenching as well as growth inhibitory effects of probucol were also examined using Chinese hamster ovary (CHO) cells in culture. In animal model, adriamycin caused a significant depression in glutathione peroxidase and increased plasma and cardiac lipids as well as lipid peroxidation. Probucol treatment modulated adriamycin-induced cardiomyopathic changes and increased glutathione peroxidase and superoxide dismutase activities. In the presence of adriamycin under hypoxic conditions, formation of adriamycin semiquinone radical was detected by ESR. The cell growth in these cultures was also inhibited by adriamycin in a dose-dependent manner. Probucol had no effect on adriamycin-induced growth inhibition as well as formation of semiquinone radicals. It is proposed that probucol protection against adriamycin cardiomyopathy is mediated by increased antioxidants and lipid-lowering without any effect on free radical production.     

The dopaminergic innervation of the intermediate lobe and of the neural lobe of the pituitary gland

The intermediate and the neural lobe of the pituitary gland are innervated by two, virtually independent, groups of dopaminergic neurons which, until recently, were considered as a uniform system and referred to as the "tubero-hypophyseal dopamine system". Some aspects of the separate physiological functions of these neurons in the intermediate and in the neural lobe, of their microanatomy and biochemistry as well as of dopamine release from their terminals are discussed in this review.     

The correction of abnormalities in the functioning of some organ systems in the case of metabolic syndrome

We studied a group of workers from one of the aircraft factories in Moscow. All of them were given a diagnosis of metabolic syndrome. We detected the abnormalities in lipidic and carbohydrate metabolisms, essential hypertension, abdominal obesity, and changes in hemostasis and fibrinolysis systems, as well as anomalies in some biochemical blood values. The patients were given the therapy of eicozyme-10 with eikonole, coenzyme Q10 and vitamin E for two months. Many values of the studied organism systems improved as a result of the medical treatment as well as the general state of patients.     

唐古特白刺单果优株果序性状变异研究

依据单果大小和口感等指标选择出39个唐古特白刺(Nitraria tangutorum Bobr．)果用优株。并以此为试验材料进一步就果序性状变异进行了研究,结果表明：白刺中选优株的果大小、果重、核果比等单果性状株间差异显著,而株内变异较小。在白刺天然群体内,果序性状差异极为显著,其中不乏果序重突出的单株。中选优株B12、B19等的平均果序重可达8．260g和8．271g,分别比对照高出6．86倍、6．87倍;比39个中选优株的平均值超出1．26倍、1．29倍。尽管白刺株内果序重变幅较大,但B12、B19的果序重最小值仍远远高出对照,甚至分别高出39株平均值79％和66％。由于与果序重密切相关的每序核果数与单果重等单果性状相对独立,因此从果用型白刺开发利用角度考虑,与产量相关更为紧密的果序重应该作为白刺优株选择以及亲本选择的主要依据。     

Schizodeme and zymodeme characterization of Leishmania in the investigation of foci of visceral and cutaneous leishmaniasis

Leishmania parasites were isolated from humans and canines in foci of cutaneous and visceral leishmaniasis. After in vitro cultivation the parasites were examined by the following biochemical techniques: (i) restriction analysis of kinetoplast DNA (kDNA) also known as schizodeme analysis (Morel et al., 1980); (ii) zymodeme analysis (Barret et al., 1980); by agarose gel electrophoresis and (iii) isoelectricfocusing in polyacrylamide gels. The strains of cutaneous and visceralizing leishmanias studied could be differentiated by schizodeme analysis, using the endonuclease MspI, into three complexes agreeing with those accepted for human New World leishmaniasis. In the municipality of Rio de Janeiro, isolates from a focus of cutaneous leishmaniasis were identified as L. braziliensis braziliensis and from a focus of visceral leishmaniasis were identified as L. donovani by zymodeme characterization. Identical restriction enzyme profiles of kDNA from human and canine isolates indicated that in the cutaneous focus at Jacarepaguá, Rio de Janeiro, the same strain was probably circulating in both the canine and human populations. This suggests a possible role for dogs as a reservoir host for L. braziliensis braziliensis. In addition, our results confirm the importance of dogs as reservoirs in visceral leishmaniasis. The stability of the electrophoretic patterns of restriction digest ("fingerprints") of Leishmania kDNA as well as differences in the sensitivity of the techniques used were demonstrated. Strains from widely different geographical areas as well as strains maintained in vivo and in vitro showed identical kDNA restriction patterns, while strains showing similar banding patterns by enzyme electrophoresis could be differentiated by schizodeme analysis. These results demonstrate the usefulness of an integrated biochemical approach in the identification of Leishmania.     

Crystal structure of cathepsin X: a flip-flop of the ring of His23 allows carboxy-monopeptidase and carboxy-dipeptidase activity of the protease

BACKGROUND: Cathepsin X is a widespread, abundantly expressed papain-like mammalian lysosomal cysteine protease. It exhibits carboxy-monopeptidase as well as carboxy-dipeptidase activity and shares a similar activity profile with cathepsin B. The latter has been implicated in normal physiological events as well as in various pathological states such as rheumatoid arthritis, Alzheimer's disease and cancer progression. Thus the question is raised as to which of the two enzyme activities has actually been monitored. RESULTS: The crystal structure of human cathepsin X has been determined at 2.67 A resolution. The structure shares the common features of a papain-like enzyme fold, but with a unique active site. The most pronounced feature of the cathepsin X structure is the mini-loop that includes a short three-residue insertion protruding into the active site of the protease. The residue Tyr27 on one side of the loop forms the surface of the S1 substrate-binding site, and His23 on the other side modulates both carboxy-monopeptidase as well as carboxy-dipeptidase activity of the enzyme by binding the C-terminal carboxyl group of a substrate in two different sidechain conformations. CONCLUSIONS: The structure of cathepsin X exhibits a binding surface that will assist in the design of specific inhibitors of cathepsin X as well as of cathepsin B and thereby help to clarify the physiological roles of both proteases.     

An application of monoclonal antibodies to identification of leptospires of serogroup icterohaemorrhagiae found in China

For the purpose of improving the procedures of identification of leptospires, a set of 5 monoclonal antibodies with different serological reactivity against serovars of Leptospira interrogans Icterohaemorrhagiae serogroup isolated in China was developed. One hundred and eight strains isolated from epidemic fields in 5 provinces in southern China were distinctly identified into 4 serovars of Icterohaemorrhagiae serogroup by the monoclonal antibody procedure, i.e., 98 isolates were identified as serovar lai, 7 as icterohaemorrhagiae, 2 as copenhageni, and 1 as H2. Factor antiserum procedure was used at the same time as control for typing these strains and an identical result was obtained.     

The effect of oxygen on fatty acid composition of soil micromycetes

The aim of this work was to describe changes in fatty acid profiles of fungi growing under artificial conditions of oxygen depletion. In total, 133 fungal strains belonging to eight orders were isolated from cattle impacted soils and tested. The analysis of the ten most frequent fatty acids revealed significant shift in fatty acids composition as a result of decreasing oxygen level. Taxonomic- as well as aeration-dependent changes in the amounts of fungal biomarker fatty acids (18:1ω9 and 18:2ω6,9) were found. Therefore, the ratio of these two fatty acids could be considered as an indicator of anaerobic, microaerobic or aerobic conditions in soil. Moreover, fatty acid-based estimation of fungal biomass in soils should be performed as a sum of both biomarker fatty acids and with respect to the soil characteristics as well as to the composition of fungal community.     

Metaphors of glaucoma

In a phenomenological study of glaucoma as an illness, 31 patients were interviewed. The goal of the study was an explication of the meanings of the experience of glaucoma, in a twofold sense: (1) the face, the role, or the self of the patient that responds to the illness; (2) the visage that the illness presents to the patient. This twofold explication was achieved by generating a classification of the interviews in terms of the dominant metaphor that emerged in each interview. The following basic metaphors are presented through case material: glaucoma as an accompaniment of aging, as blindness, as pressure, as an abstraction (and a weapon), and as fate. Variations on these themes demonstrate the necessity, in such work and for enhanced communication with patients, of paying attention to both the face that the illness presents and to the self that responds.