3+ 4/2002 - Společnost pro pojivové tkáně

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ny. After many years of endeavor compounds were tested by a drug company. After many years of endeavour the compound named STI 571 was identified that appeared to have the desired effect. Today, after some 3 years of clinical trials, STI 571 appears to induce complete remission in almost every patient with CML, even at advanced stages of the disease. There may even be hope for cure. What lessons does this story teach us? First, painstaking basic research is a prerequisite of any progress. This can best be done by academic researchers who are free to choose their projects. Second, drug development requires enormous resources that are only available to the industry. Imagination, discipline and hard core targeting is also required. Third, to get from gene discovery to therapy takes a long time. Fourth, the example shows that the scenario is possibble. It should start happening more often. My second example highlights the need of open – mindedness and imagination. Another leukemia, acute promyelocytic leukemia /APLú is often curable today through the combined use of trans – retinoic acid and chemotherapy. The disease occurs as a result of the fusion of the APL gene with the retinoic acid receptor alpha – gene. So one might think that the story resembles that of CML,the knowledge of the molecular event (in this case one interfering with the uptake of retinoic acid hinting that treatment with retinoic acid may be usefull. Not at all ! Treatment of APL with retinoic acid preceded the molecular genetic findings. It was part of Chinese folk medicine. Imagination, open mindedness and keen clinical observation are essential. How about the relatively recently detected genes that confer susceptibility to common cancers? BRC and BRCA 2 have been 122 known for approximately 7 years. Their diagnostic implications are of course huge in affected families, and testing for mutations probably leads to better risk awareness and saved lives. Like in other cancers showing Mendelian inheritance, a major benefit is to those at-risk family members who are found too be mutation negative. But unfortunately, the BRCA genes have not yet provided real breakthrougs in our understanding of pathogenetic mechanisms. Curative, non-cytotoxic drugs are but a dream. Colorectal cancer looks somewhat brighter. Here the mismatch defect caused by mutations in several genes occurs not only in the main Mendelian form of colorectal cancer (HNPCC) but also in a sizeable proportion (up to 20 %) of sporadic cancers.These mismatch – repair deficient colorectal cancer patients have a better prognosis than others. The basis of this fenomenon is not yet understood: however, epigenetic fenomena (methylation, loss of imprinting) seem to play a role. This gives hope that drugs and/or procedures may be forthcoming that interfere with these cancers. Already mismatch repair deficiency, as defined by microsatellite instability, is a tool in the large scale nolecular screening for HNPCC which in turn facilitates life-saving clinical surveillance. In summary, the detection of cancer related genes is beginning to impact the clinical handling of subsets of many cancers, but the road from gene to therapy and prevention is slow and unpredictable. GAINS AND LOSSES IN SKULL AND LIMB DEVELOPMENT A. Wilkie, Oxford LOCOMOTOR SYSTEM vol. 9, 2002, No. 3+4 In the diagnosis of syndromes, malformations of the skull and limbs frequently
occur in the same disorder.This suggest that similar molecular pathways are employed in development of these evolutionary distinct structures. These parallels will be ilustrated from work in my laboratory to elucidate the molecular basis of skull (craniosynostosis, parietal foramina) and limb (syndactyly, brachydactyly type B) malformations. These disorders commonly show dominant inheritance and the causative genes that I will discuss encode proteins of two specific categories, transcriptions factors compared to most other proteins. In contrast,diverse gain of function mechanisms (dominant positive or negative) are commonly encountered in receptor tyrosine – kinase mutations but more difficult to establish for transcription factors, although there is evidence for this type of mechanism in specific MSX 2 and HOXD13 mutations. Homozygous mutations associated with complete loss of functions are usually expected to be lethal,however in the case of ROR 2 a distinct phenotype occurs, recessive Robinow syndrome. Much remains to be learnt about how these proteins are integrated in development, but elements of a molecular pathway in the cranial suture are beginning to emerge. TRANSCRIPTION OF HOX GENES SUGGEST A LINK BETWEEN PATTERING AND THE SEGMENTATION CLOCK J. Zakany et al. Geneva, Rome During mammalian development, transcription of HOX genes is activated in presomitic mesoderm with a time sequence that follows the order of the genes along the chromosome. Consequently, newly formed somites contain specific combinations of HOX proteins, that define their fates. I shall discuss the fact that HOXD1 displays transi- tory stripes of expression within presomitic mesoderm, but not in somites. Stabilization of its transcripts through targeted modification uncovered sustained expression in somites, reminiscent of other HOX gene patterns, suggesting that cyclic activation in presomitic mesoderm may be a general phenomenon masked by slow transcript turnover. Accordingly, in addition to HOXD1 and HOXD3, we show that the promoters of both HOXB1 and HOXD11 transgenes can respond to this regulation. We propose that colinearity is associated with bursts of transcriptional activation of HOX genes every time a somite is about to form.This dynamic transcriptional behavior appears to depend upon Notch signalling, as mice deficient for the CBF 1 gene, zhe effector of the NOTCH pathway, showed severely reduced HOXD gene expression in presomitic mesoderm. These results suggest a that link between HOX gene activation and the mechanisms behind the segmentation clock. Such a linkage would coordinate the production of novel segments with their morphological specification. Pozn. Genetické studie systému HOX jsou prováděny na myších, slouží k poznání individuálního vývoje, chorob a evoluce. Existují tzv. HOX genové rodiny, sestavající z genů ABCD, které determinují umístění tělních segmentů.A je určen převážně pro kraniální oblast, ostatní pro distálnější a distální oblasti, platí systém kolinearity. HOX geny se uplatňují především na prstech. Na základě různých mutací HOX jsou sledovány různé malformace prstů u myší. Jeden typ mutace tzv. polyalaninová expanze HOX genu vyvolává u člověka tzv. II. typ synpolydaktylie, Existují rozdíly mezi homozygotním a heterozygotním fenotypem. Gradient v dávce genů HOX vede k škále fenotypů od normální pentadaktylie k adaktylii. Tyto mechanismy fungovaly již vpravěku. Pomocí mutací HOX genů lze vysvětlit POHYBOVÉ ÚSTROJÍ, ročník 9, 2002, č. 3+4 123
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S˘kora a Malík s.r.o. Technickopr
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LOCOMOTOR SYSTEM Advances in Resear
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HAJNIŠ K, SUCHOMEL A. Kolmé rozm
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EVOLUTION 1970 - 2002 6 Figure 1 Fi
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8 Figure 7 3. Growth. Figure 8. Wit
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8. Bending avoids vascular danger a
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Figure 18. Flat and hollow back, lu
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Figure 24 Figure 24. Postural repos
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Figure 30 Figure 30. Life quality.
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from papillar lines. The main appro
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a do jisté míry variabilní. Víc
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Množství faktorů formujících s
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Femur Fibula Ulna nebo Femur Tibie
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PRSTOVÉ VZORY 26 oblouk smyčka v
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TYPY ČTYŘPRSTOVÉ RÝHY 1. klasic
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Obr. 3. Příklady aplikace dermato
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LADDER Obr. 5. Žebříčkovité us
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Dermatoglyfy a geometrické znaky (
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11. Fergusson - Smith, M. A.: Karyo
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Sborník konference Biomechanika č
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90. Kuklík, M., Straus, J.: Dermat
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Obr. 7. Pacientka s oboustranným c
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involvement, those with predominant
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plastickou dysplazii (Saul-Wilson)
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- Staehling-Hampton K.,Proll S.,Pae
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Tabulka 1:Aktualizovaná klasifikac
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52 LOCOMOTOR SYSTEM vol. 9, 2002, N
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60 HNĚVKOVSKÉHO APARÁT (modifiko
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Conclusions: PCH was effective in s
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favour of DCF, which decreased to 2
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- Lequesne M., (1994) Symptomatic c
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1. ÚVOD Bolest v oblasti bederní
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analýzou k ověření jejich pevno
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Page 84 and 85: SUMMARY It is necessary by a childr
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Page 94 and 95: INTRODUCTION The perennial attentio
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Page 126 and 127: i vznik opozice palce. V experiment
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Page 142 and 143: PETRTÝL M., MAŘÍK I., - Vybraná
Page 144 and 145: MAŘÍKOVÁ O. - Symposium “Locom
Page 146 and 147: www.ortotika.cz ortotika@ortotika.c
Page 148 and 149: Tibiofemorální úhel 146 40 30 20
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Page 153 and 154: Ortopedická protetika Praha s.r.o.
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