elektronický časopis
- MeSH
- Gene Expression MeSH
- Genomics MeSH
- Conspectus
- Obecná genetika. Obecná cytogenetika. Evoluce
- NML Fields
- genetika, lékařská genetika
- NML Publication type
- elektronické časopisy
Methods in enzymology ; Vol. 200
763 s. : obr., tab., přeruš.bibliogr.
V posledních 10 letech lze zaznamenat výrazné oživení zájmu o funkční radiochirurgii. Kumulativní počty pacientů s funkčním onemocněním léčených pomocí Leksellova gama nože vzrostly ze 2 na 10 %. Tento nárůst připadá ze dvou třetin na neuralgii trojklaného nervu. Spektrum indikací funkční radiochirurgie je ale širší a objevují se nové možnosti jejího uplatnění. Indikace pro funkční radiochirurgii mohou být rozděleny do pěti skupin: léčba bolesti, pohybových extrapyramidových poruch, epilepsie, psychochirurgie a oftalmologické indikace. Protože je radiochirurgie ze své definice neinvazivní léčebnou metodou, nelze stimulačně verifikovat cíl stereotaktické operace. Proto se funkční radiochirurgie výrazně rozvíjí v indikacích, kde je cíl operace jednoznačně definovaný zobrazením pomocí magnetické rezonance, což je léčba bolesti. Významné postavení získává radiochirurgie pomocí gama nože postupně v léčbě neuralgie trigeminu, nedoceněna zůstává možnost radiochirurgické hypofyzektomie u bolestivých kostních metastáz. U pohybových poruch je radiochirurgická léčba doplňkovou metodou, protože zde je stimulační verifikace operačního cíle nejvýznamnější. V psychochirurgii vyplývá úloha radiochirurgie z celkového postavení tohoto odvětví, které je v útlumu. V epileptochirurgii je radiochirurgie prozatím ve fázi klinického experimentu. V oftalmologii se prověřuje nová perspektivní indikace, kterou je jinými metodami nezvladatelný glaukom.
During the last 10 years interest in functional radiosurgery increased markedly. Cumulative numbers of patients with functional diseases treated, using Leksell gamma knife, increased from 2 to 10%. Two-thirds of this increase are accounted for by neuralgia of the trigeminal nerve. The spectrum of indications of functional radiosurgery can be divided into five groups: treatment of pain, extrapyramidal motor disorders, epilepsy, psychosurgery and ophthalmological indications. Because radiosurgery is by definition a non-invasive therapeutic method it is not possible to verify the objective of stereotactic operations by stimulation. Therefore functional radiosurgery develops markedly in indications where the objective of surgery is unequivocally defined by visualization using magnetic resonance, i.e. treatment of pain. Radiosurgery by means of a gamma knife is gradually gaining an important position in the treatment of neuralgia of the trigeminal nerve. The possibility of radiosurgical hypophysectomy in painful osseous metastases is not appreciated sufficiently so far. In motor disorders radiosurgical treatment is a supplementary method as there verification of the objective of surgery by stimulation is most expressed. In psychosurgery the role of radiosurgery ensues from the general position of this branch which is inhibited. In epileptosurgery radiosurgery is so far in the stage of a clinical experiment. In ophthalomology a new perspective is investigated, i.e. application of radiosurgery in glaucoma resistant to other methods.
The availability of a great range of prior biological knowledge about the roles and functions of genes and gene-gene interactions allows us to simplify the analysis of gene expression data to make it more robust, compact, and interpretable. Here, we objectively analyze the applicability of functional clustering for the identification of groups of functionally related genes. The analysis is performed in terms of gene expression classification and uses predictive accuracy as an unbiased performance measure. Features of biological samples that originally corresponded to genes are replaced by features that correspond to the centroids of the gene clusters and are then used for classifier learning. Using 10 benchmark data sets, we demonstrate that functional clustering significantly outperforms random clustering without biological relevance. We also show that functional clustering performs comparably to gene expression clustering, which groups genes according to the similarity of their expression profiles. Finally, the suitability of functional clustering as a feature extraction technique is evaluated and discussed.
Practical approach series
1st ed. xviii, 253 s.
- Conspectus
- Obecná genetika. Obecná cytogenetika. Evoluce
- NML Fields
- genetika, lékařská genetika
- biologie
Sepse je závažné onemocnění s vysokou smrtností. V její patogenezi se uplatňují změny imunitní odpovídavosti hostitele od poškozující přestřelené zánětlivé odpovědi až po sekundární imunodeficienci – imunoparalýzu. Funkční stav monocytů odráží exprese HLA-DR na monocytech, infekční zánět ovlivňuje expresi CD64 na granulocytech. Oba parametry byly stanoveny u 49 pacientů v sepsi a 30 kontrolních osob pomocí nové standardizované kvantitativní metody průtokové cytometrie – QuantiBRITE, která umožňuje určit průměrný počet molekul znaku na povrchu jedné buňky. Analýza dat potvrzuje význam stanovení obou znaků u pacientů v sepsi. Exprese HLA-DR na monocytech u pacientů výrazně klesá a je jedním z faktorů spoluurčujících prognózu. Exprese CD64 na granulocytech u pacientů výrazně stoupá a koreluje s mediátory reakce akutní fáze, systémové infekce i kompenzační protizánětlivé odpovědi: interleukinem 6 (IL-6), lipopolysacharid vážícím proteinem (LBP), prokalcitoninem (PCT) a interleukinem 10 (IL-10). Oba znaky jsou přínosné především v rámci širšího panelu parametrů, při monitorování v čase a v kontextu klinického průběhu.
Background: Sepsis is a serious disease with a high case fatality rate. A variety of changes in the host immune responsiveness are observed in the pathogenesis of sepsis, ranging from detrimental hyperinflammation to profound immunoparalysis, i.e. acquired immunodeficiency. The level of monocyte HLA-DR expression reflects the functional status of monocytes as antigen-presenting cells and granulocyte CD64 expression is also indicative of infectious inflammation. Material and Methods: Monocyte HLA-DR expression and granulocyte CD64 expression were measured in 49 septic patients and 30 healthy controls using flow cytometry focused on three parameters: positive cell percentage, mean fluorescence intensity and quantitation of antibodies bound per cell (QuantiBRITE). Results: The significance of both monocyte HLA-DR expression and granulocyte CD64 expression in septic patients was confirmed. Monocyte HLA-DR dramatically decreases in septic patients compared to controls, is one of the prognostic factors and correlates with C-reactive protein. In contrast, granulocyte CD64 sharply rises in patients with sepsis and correlates with mediators of systemic inflammation (procalcitonin – PCT), proinflammatory mediators (interleukin-6 – IL-6, lipopolysaccharide binding protein – LBP) and anti-inflammatory cytokines (interleukin-10 – IL- 10). Conclusion: Quantitative monocyte HLA-DR expression and granulocyte CD64 expression are useful indicators in septic patients when considered along with the panel of other markers, monitored over a period of time and in the context of the clinical course of sepsis.
The mouse incisor is a frequently used model in studies of the molecular control of organ development. The appropriate interpretation of data on normogenesis is essential for understanding the data obtained in mutant mice. For this reason, we performed a very detailed investigation of the development of the upper incisor in wild-type mice from embryonic day (ED) 11.5 till 14.5. A combination of histology, whole mount in situ hybridization, computer-aided three-dimensional reconstructions, and fluorescent microscopy, has been used. Several sonic hedgehog (Shh) expression domains have been detected in the upper incisor region during early prenatal development. At ED11.5-13.5, there was a single Shh positive domain present in the anterior part of left or right upper jaw arches, corresponding to the epithelial thickening. More posteriorly, a new Shh expression domain appeared in the incisor bud in the developmentally more advanced ED13.5 embryos. At ED14.5, only this posterior Shh expression in the incisor germ remained detectable. This study brings new insights into the early development of the upper incisor in mice and completes the data on normal mouse incisor development. The temporal-spatial pattern of Shh expression reflects the development of two tooth generations, being detectable in two successive, antero-posteriorly located areas in the prospective incisor region in the upper jaw. The first, anterior and superficial Shh expression domain reflects the rudimentary tooth development suppressed during evolution. Only the subsequent, posterior and deeper Shh expression region, appearing at ED13.5, correlates with the prospective upper functional incisor in wild-type mice.
- MeSH
- Microscopy, Fluorescence MeSH
- Phylogeny MeSH
- In Situ Hybridization MeSH
- Maxilla embryology metabolism MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Odontogenesis MeSH
- Hedgehog Proteins genetics metabolism MeSH
- Incisor embryology metabolism MeSH
- Gene Expression Regulation, Developmental * MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Epinephrine physiology MeSH
- Receptors, Adrenergic physiology classification MeSH
- Adrenergic beta-Antagonists administration & dosage pharmacology MeSH
- Research Support as Topic MeSH
- Catecholamines physiology genetics classification MeSH
- Heart Diseases drug therapy physiopathology MeSH
- Cardiac Output, Low drug therapy physiopathology MeSH
- Norepinephrine physiology MeSH
- Receptors, Dopamine administration & dosage physiology MeSH
- Heart physiology physiopathology MeSH
BACKGROUND: Multiple myeloma (MM) is a low proliferative tumor of postgerminal center plasma cell (PC). Centrosome amplification (CA) is supposed to be one of the mechanisms leading to chromosomal instability. Also, CA is associated with deregulation of cell cycle, mitosis, DNA repair and proliferation. The aim of our study was to evaluate the prognostic significance and possible role of CA in pathogenesis and analysis of mitotic genes as mitotic disruption markers. DESIGN AND METHODS: A total of 173 patients were evaluated for this study. CD138+ cells were separated by MACS. Immunofluorescent labeling of centrin was used for evaluation of centrosome amplification in PCs. Interphase FISH with cytoplasmic immunoglobulin light chain staining (cIg FISH) and qRT-PCR were performed on PCs. RESULTS: Based on the immunofluorescent staining results, all patients were divided into two groups: CA positive (38.2%) and CA negative (61.8%). Among the newly diagnosed patients, worse overall survival was indicated in the CA negative group (44/74) in comparison to the CA positive group (30/74) (P = 0.019). Gene expression was significantly down-regulated in the CA positive group in comparison to CA negative in the following genes: AURKB, PLK4, TUBG1 (P < 0.05). Gene expression was significantly down-regulated in newly diagnosed in comparison to relapsed patients in the following genes: AURKA, AURKB, CCNB1, CCNB2, CETN2, HMMR, PLK4, PCNT, and TACC3 (P < 0.05). CONCLUSIONS: Our findings indicate better prognosis for CA positive newly diagnosed patients. Considering revealed clinical and gene expression heterogeneity between CA negative and CA positive patients, there is a possibility to characterize centrosome amplification as a notable event in multiple myeloma pathogenesis.
- MeSH
- Centrosome ultrastructure MeSH
- Adult MeSH
- In Situ Hybridization, Fluorescence MeSH
- Middle Aged MeSH
- Humans MeSH
- Mitosis MeSH
- Multiple Myeloma drug therapy genetics MeSH
- DNA Repair MeSH
- Polymerase Chain Reaction MeSH
- Prognosis MeSH
- Cell Proliferation MeSH
- Recurrence MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Cell Separation MeSH
- Gene Expression Profiling MeSH
- Syndecan-1 metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
