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  • 1
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Serine/threonine protein kinases (STPKs) represent a burgeoning concept in prokaryotic signaling and have been implicated in a range of control mechanisms. This paper describes the enzymatic and molecular characterization of PknH, a mycobacterial STPK. After cloning and expression as a Glutathione-S-transferase fusion protein in E. coli, PknH was found to phosphorylate itself and exogenous substrates like myelin basic protein and histone. The kinase activity of PknH was inhibited by the kinase inhibitors staurosporine and H-7. The results confirmed that PknH is a transmembrane protein and is restricted to members of the Mycobacterium tuberculosis complex. In addition, transcriptional analysis of pknH in M. tuberculosis under various stress conditions revealed that exposure to low pH and heat shock decreased the level of pknH transcription significantly. This is the first report describing differential expression of a mycobacterial kinase in response to stress conditions which can indicate its ability to regulate cellular events promoting bacterial adaptation to environmental change.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Anthrax toxin consists of three proteins, protective antigen, lethal factor and oedema factor. A proteolytically activated 63-kDa fragment of protective antigen binds lethal factor/oedema factor and translocates them into the cytosol. Domain II of protective antigen has been implicated in membrane insertion and channel formation. In the present study, alanine substitutions in 14 consecutive residues of the 2β1 strand that are highly homologous to the putative membrane interacting segment of Clostridium perfringens iota-b toxin were generated and the effect on the biological activity of protective antigen studied. One of the mutants, Pro260Ala, showed considerably reduced toxicity in combination with lethal factor. The mutant also showed decreased membrane insertion and translocation of lethal factor into the cytosol. The data suggest that Pro260 is important for membrane insertion and translocation by protective antigen.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Protein tyrosine kinases and tyrosine phosphatases from several bacterial pathogens have been shown to act as virulence factors by modulating the phosphorylation and dephosphorylation of host proteins. The identification and characterization of two tyrosine phosphatases namely MptpA and MptpB from Mycobacterium tuberculosis has been reported earlier. MptpB is secreted by M. tuberculosis into extracellular mileu and exhibits a pH optimum of 5.6, similar to the pH of the lysosomal compartment of the cell. To determine the role of MptpB in the pathogenesis of M. tuberculosis, we constructed a mptpB mutant strain by homologous recombination and compared the ability of parent and the mutant strain to survive intracellularly. We show that disruption of the mptpB gene impairs the ability of the mutant strain to survive in activated macrophages and guinea pigs but not in resting macrophages suggesting the importance of its role in the host–pathogen interaction. Infection of guinea pigs with the mutant strain resulted in a 70-fold reduction in the bacillary load of spleens in infected animals as compared with the bacillary load in animals infected with the parental strain. Upon reintroduction of the mptpB gene into the mutant strain, the complemented strain was able to establish infection and survive in guinea pigs at rates comparable to the parental strain. These observations demonstrate a   role   of MptpB in the pathogenesis   of M. tuberculosis.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Transition metal chemistry 11 (1986), S. 321-323 
    ISSN: 1572-901X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Dichlorobis(methylcyclopentadienyl)titanium(IV) reacts with 1,5-diarylthiocarbazones (aryl=phenyl,p-tolyl,o-chlorophenyl orp-chlorophenyl) in 1∶1 and 1∶2 molar ratios in tetrahydrofuran in the presence of triethylamine, to yield [(MeCp)2Ti(HDz)Cl], [(MeCp)2Ti(Dz)] and [(MeCp)2-Ti(HDz)2] (MeCp=methylcyclopentadienyl; HDz− and Dz2− are the mono- and di-anions of a 1,5-diarylthiocarbazone, H2Dz).S-Methyl-1,5-diphenylthiocarbazone and [(MeCp)2TiCl2] react to give [(MeCp)2Ti(MeDz)Cl] and [(MeCp)2Ti(MeDz)2] (MeDz− represents the mono-anion ofS-methyl-1,5-diphenylthiocarbazone, HMeDz) in an excess of triethylamine. These new derivatives have been characterised on the basis of elemental analyses, magnetic moment, electrical conductance, i.r.,1H n.m.r. and electronic spectral studies.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Transition metal chemistry 12 (1987), S. 335-338 
    ISSN: 1572-901X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The synthesis and characterization of the complexes from the reactions of trichloro(cyclopentadienyl)titanium(IV) with 1,5-diarylthiocarbazones (aryl=phenyl,o-tolyl,o-chlorophenyl,p-tolyl,p-chlorophenyl, or 3,5-dimethylphenyl) are reported. They are of the types CpTi(HDz)Cl2 and CpTi(HDz)2Cl (Cp=cyclopentadienyl, HDz−=the mono-anion of a 1,5-diarylthiocarbazone, H2Dz). The compounds are nonelectrolytes in dimethylformamide (DMF). In solid state, the far i.r. spectra of CpTi(HDz)Cl2 indicate the complexes to be dimeric, involving Cl-bridges.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1335
    Keywords: Shrew ; Suncus murinus ; Insectivora ; Esophageal carcinoma ; Ethanol ; MNNG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of ethanol (EtOH) on esophageal cell proliferation and the development of esophageal cancers induced byN-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in shrews were investigated. Sequential histological examination was done, and cell proliferation was assessed by BrdU labeling. At 5 weeks of age, animals were given tap water, 2% EtOH, 50 ppm MNNG, or 50 ppm MNNG plus 2%, 5% or 10% EtOH in the drinking water. Administration of 10% and 5% EtOH simultaneously with MNNG caused death in 40% (10/25) within 4 days and in 20% (6/30) within 7 days respectively, whereas other treatments were well tolerated with no sudden deaths. Administration of 2% EtOH for 30 weeks caused a 2-fold increase, and that of MNNG caused a 4.5-fold increase in the proliferation index of the basal cells of the esophagus compared with control shrews, and MNNG plus 2% EtOH caused a 5.5-fold increase. In MNNG-treated shrews, with or without 2% EtOH administration, sequential histological examination of esophageal tissue revealed a similar change; dysplasia appeared at 30 weeks of age, squamous cell carcinoma occurred at 35 weeks of age, and the depth of invasion extended to adventitia at 45 weeks of age. These finding indicate that treatment with 2% EtOH promoted the proliferation of esophageal basal cells but did not alter the tumor induction period and did not have tumor-promoting activity. EtOHper se was not carcinogenic; no tumors were seen in shrews not administered MNNG.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Bulletin of environmental contamination and toxicology 32 (1984), S. 550-556 
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-7217
    Keywords: angiogenesis inhibitor ; breast cancer ; mammary tumor ; metastasis ; TNP-470
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Antitumor and antimetastatic activity of the angiogenesis inhibitor O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), a semisynthetic analogue offumagillin, was evaluated in breast cancer cell lines. In an in vitro MTTassay, after 72 hrs continuous exposure to TNP-470, growth inhibition wasobserved in all seven cell lines of murine (JYG-A, JYG-B, DD-762, andBALB/c-MC) or human (KPL-1, MDA-MB-231, and MKL-F) origin, in which the50% inhibitory concentrations (IC50) at 72 hrstreatment were 4.6, 4.4, 4.6, 10.1, 35.0, 25.3, and 33.4 µg/ml,respectively. In an in vivo assay using JYG-A, JYG-B, KPL-1, and MDA-MB-231cells by orthotopic (right thoracic mammary fat pad) transplantation infemale nude mice, TNP-470 at 30 or 50 mg/kg body weight was injected s.c.every other day from the day of tumor cell inoculation until the end of theexperiment. The inhibitory effect on primary tumor growth was obtained inall four cell lines in a dose-dependent manner. In the 50 mg/kgTNP-470-treated group, the reductions in tumor weight of the JYG-A, JYG-B,KPL-1, and MDA-MB-231 cells with respect to the controls were 50%,30%, 4%, and 49%, respectively. Metastasis was seen inthe JYG-A, JYG-B, and KPL-1 cells. The numbers of mice bearing pulmonarymetastases of JYG-A and JYG-B cells and regional axillary lymph nodemetastases of KPL-1 cells were reduced, and TNP-470 at the 50 mg/kg dose toKPL-1 cells significantly reduced lymph node metastases compared with thecontrol. Although the weight gain was retarded in the TNP-470-treated mice,weight loss was not seen. TNP-470 was highly effective in the treatment ofbreast cancer cells. These results suggest that the clinical use of TNP-470may be a promising treatment for breast cancer patients.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 16 (2000), S. 519-521 
    ISSN: 1437-9813
    Keywords: Key words Giant omphalocele ; Exomphalos ; Silastic silo ; Abdominal wall defects ; Tissue expander
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Large omphaloceles that contain centrally herniated liver pose challenges to surgical closure, the most significant being the space limitation of the abdominal cavity. In addition, the “pedicled” nature of the liver on the inferior vena cava creates a predisposition to acute hepatic vascular outflow obstruction as the liver is reduced into the abdominal cavity. In such cases, the alternatives include conservative treatment or staged silo reduction. The worst complication of silastic silo (SS) placement is tension and infection of the fascia with disruption of the suture line. Once infection or premature disruption occurs, closure of the defect is difficult or impossible. This case report details a different management technique for a newborn with a giant omphalocele and presents an interesting variation of the usual SS technique that may be helpful in the management of some cases, especially in an emergency. The thick silk sutures applied in the present case absorbed the tension and the silastic sheet prevented the risks of infection and adhesions.
    Type of Medium: Electronic Resource
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