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Y Novik LM Ryan DG Haller R Asbury JP Dutcher A Schutt 《Cancer immunology, immunotherapy : CII》1999,16(4):261-266
The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma.
Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium.
The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with
a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m2 were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for
the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete
response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable
for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates
and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer. 相似文献
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Fabíola C Toledo Juliana E Perobelli Flávia PC Pedrosa Janete A Anselmo-Franci Wilma DG Kempinas 《Reproductive biology and endocrinology : RB&E》2011,9(1):1-9
Background
Hyperglycemia can impair the male reproductive system in experimental animals and in men during reproductive age. Studies have shown that vitamin C has some good effects on male reproductive system, and therefore vitamin C treatment could attenuate the dysfunctions in this system caused by hyperglycemia. Thus, the objective of this work was to evaluate whether vitamin C treatment could attenuate reproductive dysfunctions in hyperglycemic male rats.Methods
Adult male rats were divided into 3 groups: a normoglycemic (n = 10) and two hyperglycemic (that received a single dose of streptozotocin - 40 mg/kg BW). The two last groups (n = 10 per group) were divided into: hyperglycemic control (Hy) and hyperglycemic + 150 mg of vitamin C (HyC), by gavage during 30 consecutive days. The normoglycemic and hyperglycemic control groups received the vehicle (water). The first day after the treatment, the rats were anesthetized and killed to evaluate oxidative stress biomarkers (TBARS, SOD, GSHt and GSH-Px) in the erythrocytes, body and reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone), testicular and epididymal histo-morphometry and histopathology.Results
Compared with the normoglycemic animals, hyperglycemic control rats showed reduced weight of the body and reproductive organ but testis weight was maintained. It was also observed reduction of testosterone and LH levels, seminiferous tubular diameter, sperm motility and sperm counts in the epididymis. In addition, there was an increase in morphological abnormalities on spermatozoa as well as in oxidative stress level. Vitamin C reduced the oxidative stress level, diminished the number of abnormal sperm, and increased testosterone and LH levels and seminiferous tubular diameter but did not show improvement of sperm motility in relation to the hyperglycemic control group. Hyperglycemia caused a rearrangement in the epididymal tissue components (stroma, ephitelium and lumen) as demonstrated by the stereological analysis results. However, this alteration was partially prevented by vitamin C treatment.Conclusions
We conclude that vitamin C partially attenuated some male reproductive system dysfunctions in hyperglycemic rats. 相似文献35.
The patterns of synonymous codon usage in 91 Drosophila melanogaster genes
have been examined. Codon usage varies strikingly among genes. This
variation is associated with differences in G+C content at silent sites,
but (unlike the situation in mammalian genes) these differences are not
correlated with variation in intron base composition and so are not easily
explicable in terms of mutational biases. Instead, those genes with high
G+C content at silent sites, resulting from a strong "preference" for a
particular subset of the codons that are mostly C- ending, appear to be the
more highly expressed genes. This suggests that G+C content is reduced in
sequences where selective constraints are weaker, as indeed seen in a
pseudogene. These and other data discussed are consistent with the effects
of translational selection among synonymous codons, as seen in unicellular
organisms. The existence of selective constraints on silent substitutions,
which may vary in strength among genes, has implications for the use of
silent molecular clocks.
相似文献
36.
Molecular divergence and phylogeny: rates and patterns of cytochrome b evolution in cranes 总被引:6,自引:0,他引:6
Analyses of complete cytochrome b sequences from all species of cranes
(Aves: Gruidae) reveal aspects of sequence evolution in the early stages of
divergence. These DNA sequences are > or = 89% identical, but expected
departures from random substitution are evident. Silent, third- position
pyrimidine transitions are the dominant substitution type, with
transversion comprising only a small fraction of sequence differences.
Substitution patterns are not clearly manifested until divergence has
reached a moderate level (> 3%), as expected for a stochastic process.
Variation in the frequency of mismatch types among lineages decreases at
larger divergences, but the level of bias does not decay. Divergence varies
up to fivefold among gene regions but is not correlated with structural
domain. All protein structural domains except extramembrane 4 display <
20% variable residues. Regions corresponding to putative functional domains
show the excepted conservation of amino acids, although the C-terminal
portion of the Q0 reaction center displays several nonconservative
replacements. Phylogenetic analyses incorporating substitution asymmetries
produced mixed results. Distances estimated with multiple parameters
(transition, codon-position, composition, and pyrimidine-transition biases)
yielded identical additive tree topologies with comparable bootstrap
values, all consistent with uncontroversial species relationships. Maximum
likelihood analysis incorporating these biases, as well as equally weighted
parsimony analysis, produced similar results. Static, differential
weighting for parsimony did not improve the phylogenetic signal but
produced unusual trees with low bootstraps. The overall rate of nucleotide
substitution varies slightly but significantly among cranes, and
calibration of distances against fossil dates suggests divergence rates of
0.7%-1.7% per million years.
相似文献
37.
Evolutionary relatedness of some primate models of Plasmodium 总被引:1,自引:0,他引:1
Primate--and, specifically, monkey--malaria infections are commonly used
for understanding the pathology of and immune response to the human disease
because they are thought to resemble most closely the host-parasite
relationship found in humans. Plasmodium cynomolgi is used extensively as a
model for the human parasite, P. vivax, and P. knowlesi is used primarily
as a model for the development of erythrocytic-stage vaccines. Both of
these simian parasites can naturally infect man, resulting in mildly
symptomatic episodes of the disease. The phylogenetic relationship between
these two simian parasites and previously characterized Plasmodium species,
including P. vivax, was examined by comparison of the asexually expressed
small- subunit ribosomal RNA genes. Our analysis confirmed that P. vivax is
most closely related to P. cynomolgi and that it remains an appropriate
model of the human pathogen. Furthermore, with P. knowlesi and P. fragile,
these two species form a group of closely related species, distant from
other Plasmodium species. What is considered to be the most ancient of the
human malaria pathogens, P. malariae, was also included in the analysis and
does not group at all with other simian or human parasites.
相似文献
38.
Lathe WC rd; Burke WD; Eickbush DG; Eickbush TH 《Molecular biology and evolution》1995,12(6):1094-1105
R1 is a non-long terminal repeat (non-LTR) retrotransposable element that
inserts into a specific sequence of insect 28S ribosomal RNA genes. We have
previously shown that this element has been maintained through vertical
transmission in the melanogaster species subgroup of Drosophila. To address
whether R1 elements have been vertically transmitted for longer periods of
evolutionary time, the analysis has been extended to 11 other species from
four species groups of the genus Drosophila (melanogaster, obscura,
testecea, and repleta). All sequenced elements appeared functional on the
basis of the preservation of their open-reading frames and consistently
higher rate of substitution at synonymous sites relative to replacement
sites. The phylogenetic relationships of the R1 elements from all species
analyzed were congruent with the species phylogenies, suggesting that the
R1 elements have been vertically transmitted since the inception of the
Drosophila genus, an estimated 50-70 Mya. The stable maintenance of R1
through the germ line appears to be the major mechanism for the widespread
distribution of these elements in Drosophila. In two species, D.
neotestecea of the testecea group and D. takahashii of the melanogaster
group, a second family of R1 elements was also present that differed in
sequence by 46% and 31%, respectively, from the family that was congruent
with the species phylogeny. These second families may represent occasional
horizontal transfers or, alternatively, they could reflect the ability of
R1 elements to diverge into new families within a species and evolve
independently.
相似文献
39.
Reta-Sánchez DG JS Serrato-Corona HM Quiroga-Garza A Gaytán-Mascorro JA Cueto-Wong 《Phyton》2015,84(2):262-271
Kenaf (Hibiscus cannabinus L.) forage potential can be enhanced through its regrowth capacity and higher production in narrow rows. A field experiment was conducted in Matamoros, Coahuila, Mexico, during 2 growing seasons (2004 and 2005) to study the effects of plant height and row spacing on kenaf forage potential with multiple harvests. This study evaluated the effects of (1) 2 plant heights at cutting (1.0-1.2 m and 1.8-2.0 m) and (2) 4 inter row spacings (0.19, 0.38, 0.57 and 0.76 m) using a 2 x 4 factorial arrangement of treatments in a completely randomized block design with 4 replications. Dry matter (DM) and crude protein (CP) yields, DM partitioning, neutral detergent fiber (NDF) and CP concentrations were determined. Heights at cutting × row spacing interactions were not significant for the monitored variables (p>0.05). Kenaf response to treatments was only relevant for main effects (p≤0.05). Row spacing and plant height affected DM and CP yields (p≤0.05), whereas only plant height affected chemical composition and DM partitioning (p≤0.05). Dry matter (17.0%-26.0%), and CP (12.4%-15.6%) yields were higher (p≤0.05) when plant heights had reached 1.8 to 2.0 m. Row spacing reduction from 0.76 m to 0.38 and 0.19 m increased DM yield (20.4-33.4%) and CP yield (24.2-38.5%) (p≤0.05). Kenaf forage potential increases when planted in narrow rows and harvested 2 or 3 times during the growing season. 相似文献
40.
Though an essential trace element, manganese is generally accorded little importance in biology other than as a cofactor for some free radical detoxifying enzymes and in the photosynthetic photosystem II. Only a handful of other Mn2+-dependent enzymes are known. Recent data, primarily in bacteria, suggest that Mn2+-dependent processes may have significantly greater physiological importance. Two major classes of prokaryotic Mn2+ uptake systems have now been described, one homologous to eukaryotic Nramp transporters and one a member of the ABC-type ATPase superfamily. Each is highly selective for Mn2+ over Fe2+ or other transition metal divalent cations, and each can accumulate millimolar amounts of intracellular Mn2+ even when environmental Mn2+ is scarce. In Salmonella enterica serovar Typhimurium, simultaneous mutation of both types of transporter results in avirulence, implying that one or more Mn2+-dependent enzymes is essential for pathogenesis. This review summarizes current literature on Mn2+ transport, primarily in the Bacteria but with relevant comparisons to the Archaea and Eukaryota. Mn2+-dependent enzymes are then discussed along with some speculations as to their role(s) in cellular physiology, again primarily in Bacteria. It is of particular interest that most of the enzymes which interconvert phosphoglycerate, pyruvate, and oxaloacetate intermediates are either strictly Mn2+-dependent or highly stimulated by Mn2+. This suggests that Mn2+ may play an important role in central carbon metabolism. Further studies will be required, however, to determine whether these or other actions of Mn2+ within the cell are the relevant factors in pathogenesis. 相似文献