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961.
To ascertain the optimal treatment for carcinoma of the piriform sinus, the authors determined survival rates and local and regional tumor growth for two groups of patients: those treated by radiation therapy alone (n = 209) and those treated by radiation therapy combined with surgery (n = 154). The two groups were similar with respect to the characteristics of primary tumor stage and degree of nodal involvement. The overall 3-year and 5-year actuarial survival rates were 19.2% and 15.5%, respectively. For 5-year actuarial survival, there was no significant difference between patients with T1 and T2 tumors, but there was a significant difference between patients with T1 + T2 tumors versus those with T3 tumor. There was no significant difference in 3- and 5-year survival between patients with N0 and N1 nodal involvement and those with N1 and N2 involvement, but there was a significant difference between patients with N0 versus those with N3 involvement. The 5-year actuarial survival rate is significantly better for patients who underwent surgery followed by radiation therapy than for those who received only radiation therapy. However, for patients with early-stage (T1 and T2) tumors, radiation therapy alone controls local tumor growth as well as the combination of surgery and radiation therapy does. For each treatment group, the causes of death and patterns of failure were studied and compared with investigations to date. 相似文献
962.
963.
Mwenda JM Owuor RA Kyama CM Wango EO M'Arimi M Langat DK 《Journal of ethnopharmacology》2006,103(3):379-384
The potential effect of Khat (Catha edulis, Celastraceae) on fertility in humans has not been elucidated. In this study, we used the olive baboon (Papio anubis, Cercopithecidae) to determine the effects of oral administration of khat on circulating hormones. In order to establish baseline hormonal levels, five male baboons were bled once a week for 1 month. The same baboons were then fed with crude khat juice extract once a week over a period of 2 months, and the effects on serum levels of cortisol, testosterone and prolactin determined using enzyme immunoassay (EIA) and radioimmunoassay (RIA). Subsequently, sampling was repeated for a further 1 month to determine the residual effect of khat. The results showed that khat administration causes a significant increase in the mean levels of testosterone while prolactin and cortisol levels were reduced. These effects were also evident 1 month post treatment and indicate khat may exert a transient effect on male fertility by interfering with the hormonal profiles. 相似文献
964.
Mihalyi A Simsa P Mutinda KC Meuleman C Mwenda JM D'Hooghe TM 《Expert opinion on emerging drugs》2006,11(3):503-524
Endometriosis is a common, estrogen-dependent, gynaecological disease, defined as the presence of endometrial-like tissue outside the uterus. Although several medications are used for treatment of the disease, they are associated with high recurrence rates, considerable side effects and limited duration of application. Due to these limitations and to the impact of endometriosis on the quality of life of affected women, their environment and the society, there is a great need for new drugs able to abolish endometriosis and its symptoms. Studies in recent years investigating the (patho)physiological mechanisms involved in disease aetiology have fostered the development of novel therapeutic concepts for endometriosis, by targeting the hypothalamic-pituitary-gonadal axis, by selective modulation of estrogenic and progestogenic pathways, by inhibiting angiogenesis or by interfering with inflammatory and immunological factors. This article presents a brief summary of the currently available medications and an overview regarding the development of some of the most interesting and/or most promising novel drug candidates for endometriosis. 相似文献
965.
Kjeld?P?van Houwelingen Boukje?AC?van DijkEmail author Christina?A?Hulsbergen-van de Kaa Leo?J?Schouten Hanneke?JM?Gorissen Jack?A?Schalken Piet?A?van den Brandt Egbert?Oosterwijk 《BMC cancer》2005,5(1):57
Background
Biallelic von Hippel-Lindau (VHL) gene defects, a rate-limiting event in the carcinogenesis, occur in approximately 75% of sporadic clear-cell Renal Cell Carcinoma (RCC). We studied the VHL mutation status in a large population-based case group. 相似文献966.
Bone Mineral Density Increases in Trans Persons After 1 Year of Hormonal Treatment: A Multicenter Prospective Observational Study
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Chantal M Wiepjes Mariska C Vlot Maartje Klaver Nienke M Nota Christel JM de Blok Renate T de Jongh Paul Lips Annemieke C Heijboer Alessandra D Fisher Thomas Schreiner Guy T'Sjoen Martin den Heijer 《Journal of bone and mineral research》2017,32(6):1252-1260
Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross‐sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first‐year effects of CHT on BMD in transgender persons. A total of 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol; transmen received transdermal or intramuscular testosterone. A dual‐energy X‐ray absorptiometry (DXA) was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after 1 year of CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval [CI] 3.20 to 4.13%, p < 0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p < 0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p < 0.001) BMD was found. In transmen, TH BMD increased after 1 year of CHT (+1.04%, 95% CI 0.64 to 1.44%, p < 0.001). No changes were observed in FN BMD (–0.46%, 95% CI –1.07 to 0.16%, p = 0.144). The increase in LS BMD was larger in transmen aged ≥50 years (+4.32%, 95% CI 2.28 to 6.36%, p = 0.001) compared with transmen aged <50 years (+0.68%, 95% CI 0.19 to 1.17%, p = 0.007). In conclusion, BMD increased in transgender persons after 1 year of CHT. In transmen of postmenopausal age, the LS BMD increased more than in younger transmen, which may lead to the hypothesis that the increase in BMD in transmen is the result of the aromatization of testosterone to estradiol. © 2017 American Society for Bone and Mineral Research. 相似文献
967.
Bourgeois P; Bolcato-Bellemin AL; Danse JM; Bloch-Zupan A; Yoshiba K; Stoetzel C; Perrin-Schmitt F 《Human molecular genetics》1998,7(6):945-957
Most targeted gene mutations are recessive and analyses of gene function
often focus on homozygous mutant phenotypes. Here we describe parts of the
expression pattern of M-twist in the head of developing wild-type mice and
present our analysis of the phenotype of heterozygous twist- null animals
at around birth and in adults. A number of twist -null heterozygous mice
present skull and limb defects and, in addition, we observed other
malformations, such as defects in middle ear formation and the xyphoid
process. Our study is of interest to understand bone formation and the role
of M-twist during this process, as within the same animal growth of some
bones can be accelerated while for others it can be delayed. Moreover, we
show here that expressivity of the mouse mutant heterozygous phenotype is
dependent on the genetic background. This information might also be helpful
for clinicians, since molecular defects affecting one allele of the human
H-twist ( TWIST ) gene were identified in patients affected with
Saethre-Chotzen syndrome (SCS). Expressivity of this syndrome is variable,
although most patients present craniofacial and limb malformations
resembling those seen in mutant mice. Thus the mutant mouse twist -null
strain might be a useful animal model for SCS. The twist -null mutant mouse
model, combined with other mutant mouse strains, might also help in an
understanding of the etiology of morphological abnormalities that appear in
human patients affected by other syndromes.
相似文献
968.
Transfected Plasmodium knowlesi produces bioactive host gamma interferon: a new perspective for modulating immune responses to malaria parasites
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Ozwara H Langermans JA Kocken CH van der Wel A van der Meide PH Vervenne RA Mwenda JM Thomas AW 《Infection and immunity》2003,71(8):4375-4381
Transgenic pathogenic microorganisms expressing host cytokines such as gamma interferon (IFN-gamma) have been shown to manipulate host-pathogen interaction, leading to immunomodulation and enhanced protection. Expression of host cytokines in malaria parasites offers the opportunity to investigate the potential of an immunomodulatory approach by generating immunopotentiated parasites. Using the primate malaria parasite Plasmodium knowlesi, we explored the conditions for expressing host cytokines in malaria parasites. P. knowlesi parasites transfected with DNA constructs for expressing rhesus monkey (Macaca mulatta) IFN-gamma under the control of the heterologous P. berghei apical membrane antigen 1 promoter, produced bioactive IFN-gamma in a developmentally regulated manner. IFN-gamma expression had no marked effect on in vitro parasite development. Bioactivity of the parasite-produced IFN-gamma was shown through inhibition of virus cytopathic effect and confirmed by using M. mulatta peripheral blood cells in vitro. These data indicate for the first time that it is feasible to generate malaria parasites expressing bioactive host immunomodulatory cytokines. Furthermore, cytokine-expressing malaria parasites offer the opportunity to analyze cytokine-mediated modulation of malaria during the blood and liver stages of the infection. 相似文献
969.
Sliwinski A Stanic D Finkelstein DI Ilic M West JM Dooley PC 《Journal of muscle research and cell motility》2005,26(2-3):149-155
It is well established that mammalian skeletal muscles exhibit a considerable degree of plasticity and one of the main determining
factors of this plasticity is the activity pattern and duration of motoneurone discharge. Lesions to the right substantia
nigra pars compacta (SNpc) of six adult rats were made to determine whether altered output from the SNpc ultimately leads
to a change in the expression of proteins in contralateral skeletal muscles. After 4 months, altered motor performance was
identified by the administration of amphetamine. After 7 months, 30–70% of dopaminergic cells in the SNpc had been destroyed.
The protein content of muscles was then quantified from densitometric scans of gels, and expressed as a % of the amount of
actin (the protein used as a reference in this study). The lesion affected the expression of different protein isoforms in
the fast- and slow-twitch muscles. In slow-twitch soleus muscles, the lesion decreased the proportion of α-tropomyosin and
increased the proportion of β-tropomyosin. In the fast-twitch extensor digitorum longus muscles, the lesion increased the
proportion of the fast isoform of troponin-T1f, and decreased the proportions of the two isoforms of myosin light chain. This study establishes a connection between the
chronic effects of a lesion to the SNpc, with a loss of dopaminergic neurones, impaired motor performance, and altered expression
of proteins in skeletal muscle. The implication of these results is that the altered motor function observed in Parkinson’s
disease may be associated with alterations to the expression of skeletal muscle proteins.
Supported by grants from NH & MRC (DF) and Faculty of Health Sciences, LaTrobe University (PD). 相似文献
970.
Takahiro Taguchi Kunihiro Akimaru Hirohisa Hirai Yuriko Hirai Jason M. Mwenda Kazunari Yuri 《Chromosome research》2003,11(2):147-152
We isolated a DNA probe, designated MMDYZ1, using a chromosome microdissection technique from the Y chromosome of the Rhesus monkey. The probe obtained from eight whole Y chromosomes shows higher specificity for the Y short arm of the Rhesus monkey, which consists totally of constitutive heterochromatin. Two microclones (MMY#3 and MMY#4) were constructed from the Y-specific primary PCR products. Sequence analysis of these two microclones revealed that both were essentially identical to each other and the sizes were 870 and 686bp, respectively. From alignment analysis using the Genbank database of primates, the alphoid DNA has the highest affinity with the probe. However, the total composition of this probe has extremely high homology with the Y short arm of the Rhesus monkey, as demonstrated by fluorescence in-situ hybridization (FISH). Comparative FISH-mapping disclosed that this DNA-sequence cluster was located at extremely different sites on the Y chromosome in several species of the Old World monkey. Accordingly, this probe seems to be a high-quality tool, now established for the first time, for investigating Y chromosome evolution of the Old World monkey. 相似文献