Chu, D K* Dotaz Zobrazit nápovědu
STR/N is an inbred strain of mice which is known to exhibit extreme polydipsia and polyuria. We previously found central administration of angiotensin II enhanced cardiovascular responses in STR/N mice than normal mice, suggesting that STR/N mice might exhibit different cardiovascular responses. Therefore, in this study, we investigated daily mean arterial blood pressure and heart rate, and changes in the baroreceptor-heart rate reflex in conscious STR/N mice and control (ICR) mice. We found that variability in daily mean arterial blood pressure and heart rate was significantly larger in STR/N mice than in ICR mice (p<0.05). There was a stronger response to phenylephrine (PE) in STR/N mice than in ICR mice. For baroreceptor reflex sensitivity, in the rapid response period, the slopes of PE and sodium nitroprusside (SNP) were more negative in STR/N mice than in ICR mice. In the later period, the slopes of PE and SNP were negatively correlated between heart rate and blood pressure in ICR mice, but their slopes were positively correlated in STR/N mice. These results indicated that STR/N mice exhibited the different cardiovascular responses than ICR mice, suggesting that the dysfunction of baroreceptor reflex happened in conscious STR/N mice.
- MeSH
- baroreflex účinky léků MeSH
- fenylefrin farmakologie MeSH
- krevní tlak MeSH
- myši inbrední ICR MeSH
- myši MeSH
- nitroprusid farmakologie MeSH
- polydipsie genetika patofyziologie MeSH
- presoreceptory patofyziologie MeSH
- srdeční frekvence * účinky léků MeSH
- vazodilatancia farmakologie MeSH
- vazokonstriktory farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Toxins are produced by bacteria, plants and animals for defense or for predation. Most of the toxins specifically affect the mammalian nervous system by interfering with the transmission of nerve impulses, and such toxins have the potential for misuse by the military or terrorist organizations. This review discusses the origin, structure, toxicity and symptoms, transmission, mechanism(s) of action, symptomatic treatment of the most important toxins and venoms derived from fungi, plants, marine animals, and microorganisms, along with their potential for use in bioweapons and/or biocrime. Fungal trichothecenes and aflatoxins are potent inhibitors of protein synthesis in most eukaryotes and have been used as biological warfare agents. Ricin and abrin are plant-derived toxins that prevent the elongation of polypeptide chains. Saxitoxin, anatoxin, and tetrodotoxin are marine-derived toxins that bind to sodium channels in nerve and muscle tissue and cause muscle paralysis. Most bacterial toxins, such as botulinum and Shiga affect either the nervous system (neurotoxins) or damage cell membranes. Batrachotoxins, which are secreted by poison-dart frogs are extremely potent cardiotoxic and neurotoxic steroidal alkaloids. The aim of this review is to provide basic information to enable further understanding of these toxins and their potential military uses.
- MeSH
- abrin chemie otrava škodlivé účinky MeSH
- aflatoxiny chemie otrava škodlivé účinky MeSH
- bakteriální toxiny otrava MeSH
- batrachotoxiny chemie otrava škodlivé účinky MeSH
- biologické bojové látky * MeSH
- biologické toxiny * otrava škodlivé účinky MeSH
- botulotoxiny chemie otrava škodlivé účinky MeSH
- lidé MeSH
- mořské toxiny otrava MeSH
- mykotoxiny otrava škodlivé účinky MeSH
- otrava * prevence a kontrola terapie MeSH
- ricin chemie otrava škodlivé účinky MeSH
- saxitoxin chemie otrava škodlivé účinky MeSH
- shiga toxiny chemie otrava škodlivé účinky MeSH
- T-2 toxin chemie otrava škodlivé účinky MeSH
- tetrodotoxin chemie otrava škodlivé účinky MeSH
- toxoidy otrava škodlivé účinky MeSH
- živočišné jedy otrava škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
A two-component CD20 (non-internalizing) receptor crosslinking system based on the biorecognition of complementary coiled-coil forming peptides was evaluated. Exposure of B cells to Fab'-peptide1 conjugate decorates the cell surface with peptide1; further exposure of the decorated cells to P-(peptide2)x (P is the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone) results in the formation of coiled-coil heterodimers at the cell surface with concomitant induction of apoptosis. The aim of this study was to determine the potential immunogenicity of this therapeutic system that does not contain low molecular weight drugs. Enantiomeric peptides (L- and D-CCE and L- and D-CCK), HPMA copolymer-peptide conjugates, and Fab' fragment-peptide conjugates were synthesized and the immunological properties of peptide conjugates evaluated in vitro on RAW264.7 macrophages and in vivo on immunocompetent BALB/c mice. HPMA copolymer did not induce immune response in vitro and in vivo. Administration of P-peptide conjugates with strong adjuvant resulted in antibody response directed to the peptide. Fab' was responsible for macrophage activation of Fab'-peptide conjugates and a major factor in the antibody induction following i.v. administration of Fab'-conjugates. There was no substantial difference in the ability of conjugates of D-peptides and conjugates of L-peptides to induce Ab response.
- MeSH
- akrylamidy aplikace a dávkování chemie imunologie MeSH
- buněčné linie MeSH
- imunoglobuliny - Fab fragmenty aplikace a dávkování chemie imunologie MeSH
- makrofágy účinky léků imunologie MeSH
- molekulární sekvence - údaje MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- peptidy aplikace a dávkování chemie imunologie MeSH
- sekvence aminokyselin MeSH
- T-lymfocyty účinky léků imunologie MeSH
- tvorba protilátek účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Seven new species of chewing lice in the genus Resartor Gustafsson et Bush, 2017 are described and illustrated. They are: Resartor albofulvus sp. n. ex Heterophasia desgodinsi desgodinsi (Oustalet); Resartor apimimus sp. n. ex Heterophasia picaoides wrayi (Ogilvie-Grant); Resartor aterrimus sp. n. ex Minla ignotincta mariae La Touche; Resartor extraneus sp. n. ex Lioparus chrysotis swinhoii (Verreaux); Resartor guangxiensis sp. n. ex Trochalopteron milnei sinianum Stresemann; Resartor longisuturalis sp. n. ex Actinodura cyanouroptera wingatei (Ogilvie-Grant); Resartor seminudus sp. n. ex Leiothrix argentauris tahanensis (Yen). All species differ in the shape of the head, shape of the male genitalia and abdominal chaetotaxy. A checklist and a key to the species of Resartor are provided.
- MeSH
- Ischnocera klasifikace fyziologie MeSH
- nemoci ptáků parazitologie MeSH
- zavšivení parazitologie veterinární MeSH
- zpěvní ptáci * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Čína MeSH
- Malajsie MeSH
Neurofibromatosis type 2 (NF-2) is a dominantly inherited genetic disorder that results from variants in the tumor suppressor gene, neurofibromin 2 (NF2). Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by inducible genetic knockout of nf2a/b, the zebrafish homologs of human NF2. Analysis of nf2a and nf2b expression revealed ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, nf2a displayed lower expression levels. Induction of nf2a/b knockout at early stages increased the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a/b knockout triggered the development of a spectrum of tumors, including vestibular Schwannomas, spinal Schwannomas, meningiomas and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.
- MeSH
- dánio pruhované * genetika embryologie MeSH
- geneticky modifikovaná zvířata MeSH
- genový knockout * MeSH
- larva metabolismus MeSH
- lidé MeSH
- modely nemocí na zvířatech * MeSH
- neurofibromatóza 2 genetika patologie metabolismus MeSH
- neurofibromatózy genetika patologie metabolismus MeSH
- neurofibromin 2 * genetika metabolismus nedostatek MeSH
- proliferace buněk MeSH
- proteiny dánia pruhovaného * genetika metabolismus nedostatek MeSH
- Schwannovy buňky metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: To test the performance of an oral cancer prognostic 13-gene signature for the prediction of survival of patients diagnosed with HPV-negative and p16-negative oral cavity cancer. MATERIALS AND METHODS: Diagnostic formalin-fixed paraffin-embedded oral cavity cancer tumor samples were obtained from the Fred Hutchinson Cancer Research Center/University of Washington, University of Calgary, University of Michigan, University of Utah, and seven ARCAGE study centers coordinated by the International Agency of Research on Cancer. RNA from 638 Human Papillomavirus (HPV)-negative and p16-negative samples was analyzed for the 13 genes using a NanoString assay. Ridge-penalized Cox regressions were applied to samples randomly split into discovery and validation sets to build models and evaluate the performance of the 13-gene signature in predicting 2-year oral cavity cancer-specific survival overall and separately for patients with early and late stage disease. RESULTS: Among AJCC stage I/II patients, including the 13-gene signature in the model resulted in substantial improvement in the prediction of 2-year oral cavity cancer-specific survival. For models containing age and sex with and without the 13-gene signature score, the areas under the Receiver Operating Characteristic Curve (AUC) and partial AUC were 0.700 vs. 0.537 (p < 0.001), and 0.046 vs. 0.018 (p < 0.001), respectively. Improvement in predicting prognosis for AJCC stage III/IV disease also was observed, but to a lesser extent. CONCLUSIONS: If confirmed using tumor samples from a larger number of early stage oral cavity cancer patients, the 13-gene signature may inform personalized treatment of early stage HPV-negative and p16-negative oral cavity cancer patients.
- MeSH
- analýza přežití MeSH
- dospělí MeSH
- fixace tkání MeSH
- inhibitor p16 cyklin-dependentní kinasy metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidský papilomavirus 16 izolace a purifikace MeSH
- mladý dospělý MeSH
- nádorové biomarkery genetika MeSH
- nádory úst genetika metabolismus patologie MeSH
- plocha pod křivkou MeSH
- sekvenční analýza RNA MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom genetika metabolismus patologie MeSH
- staging nádorů MeSH
- stanovení celkové genové exprese metody MeSH
- zalévání tkání do parafínu MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Investigations into the chemical constituents of the seeds of the neglected tuber crop Pachyrhizus tuberosus (Leguminosae) resulted in the isolation of seven components: five rotenoids [12a-hydroxyerosone (1), 12a-hydroxydolineone (2), erosone (3), 12a-hydroxyrotenone (4) and rotenone (6)], a phenylfuranocoumarin [pachyrrhizine (5)] and an isoflavanone [neotenone (7)]. The compounds were isolated using several chromatography techniques and characterized and verified by NMR and HPLC/MS. The MTT assay was used to examine the selective cytotoxic effects of the methanolic P. tuberosus extract and isolated compounds in two human cancer cell lines [breast (MCF-7) and colorectal (HCT-116)] and in non-transformed human fibroblasts (MRC-5); IC50 values were calculated. The methanolic P. tuberosus extract displayed respectable cytotoxic effects against HCT-116 and MCF-7 cells with IC50 values of 7.3 and 6.3 microg/mL, respectively. Of the compounds, 6 exacted greatest cytotoxicity and selectivity towards the cancer cell lines tested, yielding IC50 values of 0.3 microg/mL against both MCF-7 and HCT-116 cells, and a 6-fold reduced activity against MRC-5 fibroblasts. Compound 4 also demonstrated cytotoxicity against MCF-7 and HCT-116 (1.1 and 1.8 microg/mL, respectively), and reduced cytotoxicity towards MRC-5 cells (7.5 mirog/mL). The results revealed from the in vitro cytotoxic MTT assay are worthy of further antitumor investigation.
- MeSH
- antitumorózní látky fytogenní chemie izolace a purifikace MeSH
- HCT116 buňky MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- molekulární struktura MeSH
- Pachyrhizus chemie MeSH
- rotenon analogy a deriváty chemie izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH